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(1) Background: Atherosclerosis is a leading cause of vascular death worldwide. High urinary phosphate has recently been identified as a cardiovascular risk factor, but its role has not been fully established. The aim of this study was to investigate the association between urinary phosphate and subclinical atherosclerosis in the carotid, femoral as well as coronary territories; (2) Methods: We performed a cross-sectional analysis of a sample of 1169 middle-aged men, aged 50.9 years (SD 3.7), without previous cardiovascular disease, belonging to the Aragon Workers Health Study (AWHS). Urinary phosphate was analyzed in urine samples using the Fiske-Subbarow method. The presence of carotid plaque and femoral plaque was assessed by ultrasound and coronary artery calcium score (CACS) by computed tomography. Demographic, anthropometric and clinical data were collected at annual medical examinations. Logistic regression models were used to estimate the prevalence of adjusted atherosclerosis in the different vascular arteries; (3) Results: A significant inverse association was observed between urinary phosphate and subclinical atherosclerosis in the carotid [OR 95% CI 0.69 (0.49–0.99)] and coronary (CACS > 200) [OR 95% CI 0.46 (0.23–0.88)] arteries; however, no statistically significant association was found between urinary phosphate and the presence of atheroma plaques in the femoral territory [OR 1.02 (0.72–1.45)]; (4) Conclusions: In middle-aged men, a higher urinary phosphate concentration is associated with a lower prevalence of subclinical carotid and coronary atherosclerosis compared with those with a lower urinary phosphate concentration. [ABSTRACT FROM AUTHOR]

Abstract Background With the emergence of photon-counting CT, ultrahigh-resolution (UHR) imaging can be performed without dose penalty. This study aims to directly compare the image quality of UHR and standard resolution (SR) scan mode in femoral artery angiographies. Methods After establishing continuous extracorporeal perfusion in four fresh-frozen cadaveric specimens, photon-counting CT angiographies were performed with a radiation dose of 5 mGy and tube voltage of 120 kV in both SR and UHR mode. Images were reconstructed with dedicated convolution kernels (soft: Body-vascular (Bv)48; sharp: Bv60; ultrasharp: Bv76). Six radiologists evaluated the image quality by means of a pairwise forced-choice comparison tool. Kendall’s concordance coefficient (W) was calculated to quantify interrater agreement. Image quality was further assessed by measuring intraluminal attenuation and image noise as well as by calculating signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNR). Results UHR yielded lower noise than SR for identical reconstructions with kernels ≥ Bv60 (p

Background: With the emergence of photon-counting CT, ultrahigh-resolution (UHR) imaging can be performed without dose penalty. This study aims to directly compare the image quality of UHR and standard resolution (SR) scan mode in femoral artery angiographies. Methods: After establishing continuous extracorporeal perfusion in four fresh-frozen cadaveric specimens, photon-counting CT angiographies were performed with a radiation dose of 5 mGy and tube voltage of 120 kV in both SR and UHR mode. Images were reconstructed with dedicated convolution kernels (soft: Body-vascular (Bv)48; sharp: Bv60; ultrasharp: Bv76). Six radiologists evaluated the image quality by means of a pairwise forced-choice comparison tool. Kendall's concordance coefficient (W) was calculated to quantify interrater agreement. Image quality was further assessed by measuring intraluminal attenuation and image noise as well as by calculating signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNR). Results: UHR yielded lower noise than SR for identical reconstructions with kernels ≥ Bv60 (p < 0.001). UHR scans exhibited lower intraluminal attenuation compared to SR (Bv60: 406.4 ± 25.1 versus 418.1 ± 30.1 HU; p < 0.001). Irrespective of scan mode, SNR and CNR decreased while noise increased with sharper kernels but UHR scans were objectively superior to SR nonetheless (Bv60: SNR 25.9 ± 6.4 versus 20.9 ± 5.3; CNR 22.7 ± 5.8 versus 18.4 ± 4.8; p < 0.001). Notably, UHR scans were preferred in subjective assessment when images were reconstructed with the ultrasharp Bv76 kernel, whereas SR was rated superior for Bv60. Interrater agreement was high (W = 0.935). Conclusions: Combinations of UHR scan mode and ultrasharp convolution kernel are able to exploit the full image quality potential in photon-counting CT angiography of the femoral arteries. Relevance statement: The UHR scan mode offers improved image quality and may increase diagnostic accuracy in CT angiography of the peripheral arterial runoff when optimized reconstruction parameters are chosen. Key points: • UHR photon-counting CT improves image quality in combination with ultrasharp convolution kernels. • UHR datasets display lower image noise compared with identically reconstructed standard resolution scans. • Scans in UHR mode show decreased intraluminal attenuation compared with standard resolution imaging. [ABSTRACT FROM AUTHOR]

Aim. To identify and characterize the associations of the presence and severity of atherosclerosis of various localization with the blood level of biochemical parameters, as well as to assess the potential of their use as markers of metabolic disorders with increased atherogenic potential.Material and methods. The study included 216 patients (men, 53%) aged 24-87 years (mean age, 61,5±10,73 years). All patients underwent coronary angiography, carotid (CA) and femoral arterial (FA) duplex ultrasound to assess the presence and severity of atherosclerosis. In blood serum/plasma, biochemical parameters were analyzed using standard methods.Results. Based on the analysis of circulating biomarker profile, diagnostic complexes have been established that allow assessing atherosclerosis of different localization. According to the data obtained, the determinants of coronary and CA atherosclerosis are endothelial dysfunction (concentration of nitric oxide metabolites

Aim. To study the prevalence of carotid (CA) and femoral artery (FA) atherosclerosis among Russian population, mainly in middle age group, using a representative sample of one of the Central Russian regions.Material and methods. The analysis included participants of the ATEROGEN-Ivanovo study (sub-study of the ESSE-RF conducted in the Ivanovo region) aged 40-67 years, who were invited for CA and FA ultrasound to assess plaque presence. A total 1102 people were examined, which was >80% of the original sample.Results. The age of subjects was 54 [48; 60] years (men, 28%). Only 11,2% of participants took statins; 30,9% had low cardiovascular risk (CVR), 35,6% — moderate CVR, 21,8% — high CVR, and 11,8% — very high CVR. The incidence of at least one plaque in CA or FA was 73,6%. The prevalence of CA atherosclerosis was 76,4% in men and 59,1% in women, FA atherosclerosis — 54,9% and 28,3%, respectively. Furthermore, plaques were detected already at the age of 40. The incidence of plaques significantly increased with age, with the exception of carotid atherosclerosis in men, a significant increase in the incidence of which stopped at 45 years of age.Conclusion. Among the Ivanovo population aged 40-67 with a predominance of low-to-moderate CVR patients, there is a high prevalence of carotid and femoral atherosclerosis, which indicates a high potential for using ultrasound for diagnosing subclinical atherosclerosis in assessing CVR in people of this age range.

Aim. To study the effectiveness of determining atherosclerosis and its severity in the brachiocephalic (BCA), coronary (CA) and femoral (FA) arteries based on the endothelial function test proposed by Celermajer DS.Material and methods. The study included 216 patients: 115 men and 101 women aged 24-87 years (mean age, 61,5±10,73 years). All patients underwent coronary angiography to assess the presence and severity of coronary artery atherosclerosis, and duplex ultrasound of BCA and FA atherosclerosis. The functional activity of the endothelium was assessed using the Celermajer test.Results. Depending on the presence and severity of atherosclerosis in each arterial region (BCA, CA and FA), patients were divided into the following groups: group 1 — patients with intact arteries, group 2 — patients with moderate atherosclerosis, group 3 — patients with severe atherosclerosis. Comparative analysis of brachial artery diameters identified by the Celermajer test revealed a significant difference between the groups. Comparison of Celermajer test results in CA groups was as follows: groups 1 and 2 (p=0,34), groups 1 and 3 (p

Currently, the concept of atherosclerosis has undergone a number of changes. On the one hand, carotid atherosclerosis, like femoral, is a disease that must be treated directly, and on the other hand, it is a modifier of cardiovascular risk. This review is devoted to aspects of cardiovascular risk stratification depending on the severity and progression of carotid and femoral artery atherosclerosis.

More than a half of cardiovascular events occur in low to moderate cardiovascular risk patients if assessed based on the traditional risk factors. At the same time, ultrasound examination of arteries makes it possible to reveal atherosclerosis even at early stages of its development. High prevalence of subclinical atherosclerosis in low to moderate risk patients, which is a realization of traditional and “unknown” risk factors, makes ultrasound examination a useful method for risk stratification. The review is focused on ultrasound markers of atherosclerosis with association to traditional risk factors, on the possibility to improve predictive role of current scores and influence on outcomes. Predictive significance of the markers is regarded for primary prevention in general population, in high risk persons and from the perspective of quantitative indicator of atherosclerotic lesion grade or plausibility as a surrogate cardiovascular diseases marker.

Background: The soluble urokinase plasminogen activator receptor (suPAR) is related to hepatic inflammation and fibrosis and has been suggested to participate in the development of liver cirrhosis. Therefore, the aim of the current study was to measure the concentration of suPAR in the hepatic vein of cirrhotic patients during a liver vein catheterization to identify a possible hepatic suPAR generation. Furthermore, we explored if suPAR levels were associated with the degree of cirrhosis and liver dysfunction. Methods and patients: We included 105 cirrhotic patients and 19 liver-healthy controls. Blood was sampled from the hepatic vein and the femoral artery and suPAR was measured by enzyme-linked immunosorbent assay. Results: We identified significantly higher median suPAR concentrations among the cirrhotic patients (7.2 ng/ml in the hepatic vein; 6.8 ng/ml in the femoral artery) compared to the controls (2.6 ng/ml, respectively, p-values <0.001). However, the median hepatic suPAR formation was 0.0 ng/ml in both groups. We observed significantly increasing suPAR levels according to higher Child classes (4.5 ng/ml, 6.9 ng/ml and 9.0 ng/ml, Child A, B, C respectively; p-value<0.001), and significantly higher median suPAR concentrations in patients with ascites versus patients without ascites (8.1 ng/ml versus 5.3 ng/ml, respectively, p-value<0.001). suPAR levels were significantly related to bilirubin (r = 0.48, p<0.001), the hepatic venous pressure gradient (r = 0.39, p<0.001), the cardiac index (r = 0.24, p = 0.02) and the plasma volume (r = 0.33, p = 0.001), whereas suPAR levels were significantly inversely related to albumin (r = -0.59, p<0.001), plasma coagulation factors (r-0.39, p<0.001), the mean arterial pressure (r = -0.28, p = 0.004), the systemic vascular resistance (r = 0.26, p = 0.007), the indocyanine green clearance (r = -0.51, p<0,001) and the galactose elimination capacity (r = -0.39, p<0.001). Conclusion: We identified elevated suPAR concentration in cirrhotic patients, which correlated significantly with the degree of cirrhosis and liver failure, but we were not able to demonstrate hepatic suPAR generation per se. This suggests that further investigations of the source of suPAR in cirrhotic patients need to be undertaken. [ABSTRACT FROM AUTHOR]

Background: Many studies found increased central arterial stiffness and poor endothelial function in patients with coronary artery disease (CAD). Acute exercise has been shown to decrease peripheral pulse wave velocity (pPWV) in young healthy volunteers. We hypothesized the response to acute exercise to be diminished in CAD patients compared to healthy young (HY) and age-matched (HAM) controls. Methods: In 21 patients after recent myocardial infarction (CAD), 11 HAM and 10 HY pPWV was measured by applanation tonometry at the proximal femoral artery and the posterior tibial artery at rest and from 5 to 15 min after cessation of exhaustive exercise. Heart rate (HR) and blood pressure (BP) were monitored continuously. Resting central PWV (cPWV) was measured between the carotid and femoral arteries. Resting values and reponses to acute exercise were compared between the three groups and predictors for pPWV response were sought. Results: The response in pPWV to acute exercise seen in HY (lowering in pPWV by 17%) was absent in both CAD and HAM. Resting pPWV was not statistically different between the three groups, while cPWV was comparable in CAD and HAM but 17% lower in HY. Predictors for response in pPWV to exercise were age (Spearman r = 0.48), cPWV (r = 0.34) and response in diastolic BP (r = 0.32). Conclusion: The response in pPWV to acute exercise observed in HY was absent in CAD and HAM. In dilated peripheral arteries, PWV may reflect stiffness of passive vessel structures, which are likely to increase with age in healthy persons and CAD alike. [ABSTRACT FROM AUTHOR]

Background: The sensitivity and specificity of exercise testing have never been studied simultaneously against an objective quantification of arterial stenosis. Aims were to define the sensitivity and specificity of several exercise tests to detect peripheral artery disease (PAD), and to assess whether or not defined criteria defined in patients suspected of having a PAD show a difference dependent on the resting ABI. Methods: In this prospective study, consecutive patients with exertional limb pain referred to our vascular center were included. All patients had an ABI, a treadmill exercise-oximetry test, a second treadmill test (both 10% slope; 3.2km/h speed) with post-exercise pressures, and a computed-tomography-angiography (CTA). The receiver-operating-characteristic curve was used to define a cut-off point corresponding to the best area under the curve (AUC; [CI95%]) to detect arterial stenosis ≥50% as determined by the CTA. Results: Sixty-three patients (61+/-11 years-old) were included. Similar AUCs from 0.72[0.63–0.79] to 0.83[0.75–0.89] were found for the different tests in the overall population. To detect arterial stenosis ≥50%, cut-off values of ABI, post-exercise ABI, post-exercise ABI decrease, post-exercise ankle pressure decrease, and distal delta from rest oxygen pressure (DROP) index were ≤0.91, ≤0.52, ≥43%, ≥20mmHg and ≤-15mmHg, respectively (p<0.01). In the subset of patients with an ABI >0.91, cut-off values of post-exercise ABI decrease (AUC = 0.67[0.53–0.78]), and DROP (AUC = 0.67[0.53–0.78]) were ≥18.5%, and ≤-15mmHg respectively (p<0.05). Conclusion: Resting ABI is as accurate as exercise testing in patients with exertional limb pain. Specific exercise testing cut-off values should be used in patients with normal ABI to diagnose PAD. [ABSTRACT FROM AUTHOR]

Background: Aortic stiffness is an independent predictor of cardiovascular morbidity and mortality; thus, simple, rapid and preferably automated techniques are indispensable for pursuing a global risk stratification approach. We present an oscillometric technique for determination of the carotid-femoral pulse wave velocity (cfPWV), including the diagnostic accuracy, sensitivity and specificity, with emphasis on the training curve and procedural duration. Methods: In a single-centre crossover study, we evaluated subjects free of known cardiovascular disease (CVD), subjects with CVD and a subgroup of subjects with peripheral artery disease (PAD) in terms of ankle-brachial index (ABI) and PWV measurements determined by oscillometry compared to tonometry. Pearson’s correlation analysis was used to assess the relationship of the PWV measurements determined by both methods. Moreover, the time and cost of the examinations were compared. Results: A total of 176 study subjects underwent assessments to obtain oscillometric and tonometric PWV measurements. The CVD-free subjects (n = 59) were younger (60.4±15.6 vs. 67.5±12.9 years, p = 0.003) than the subjects with CVD (n = 117). The PWV measurements showed significant correlations in CVD-free subjects (r = 0.797, p<0.001), in subjects with CVD (r = 0.817, p<0.001) and in the subgroup of subjects with PAD (r = 0.807, p<0.001). The examination duration was shorter for the oscillometric method than the tonometric method (4.4±0.5 vs. 9.2±0.8 min, p<0.001). Conclusion: Using a simple and rapid automated oscillometric method, we achieved good diagnostic accuracy for the determination of aortic stiffness through the PWV in both subjects with and without CVD. This method might be helpful in daily practice in terms of saving time and reducing procedural complexity for screening for cardiovascular morbidities and vascular damage in cases of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is associated with an increased risk of cardiovascular disease (CVD) at younger ages that is not identifiable by traditional risk factors. Screening for subclinical atherosclerosis with ultrasound has only been investigated in carotid arteries. Femoral artery ultrasound has never been considered for this purpose. The link between psoriasis and accelerated atherosclerosis has not yet been established. Objective: To study the usefulness of femoral artery ultrasound for the detection of subclinical atherosclerosis in psoriasis. We also investigated its possible relationship with changes in insulin resistance. Methods: We conducted a cross-sectional study in 140 participants, 70 patients with moderate-to-severe psoriasis and 70 healthy controls, matched 1:1 for age, sex, and BMI. Femoral and carotid atherosclerotic plaques were evaluated by ultrasonography. Insulin resistance was assessed by the homeostasis model assessment method (HOMA-IR). Results: Femoral atherosclerotic plaque prevalence was significantly higher in patients with psoriasis (44.64%) than in controls (19.07%) (p<0.005), but no significant difference was found in carotid plaque prevalence (p<0.3). Femoral plaques were significantly more prevalent than carotid plaques (21.42%) among patients with psoriasis (p<0.001). In the regression analysis, insulin resistance was the most influential determinant of atherosclerosis in psoriasis and C-reactive protein the most significant predictor of insulin resistance. Conclusions: Ultrasound screening for femoral atherosclerotic plaques improves the detection of subclinical atherosclerosis in patients with psoriasis, whereas the study of carotid arteries is not sufficiently accurate. Insulin resistance appears to play a greater role in the development of atherosclerosis in these patients in comparison to other classical CVD risk factors. [ABSTRACT FROM AUTHOR]

Background: Repair of acute type A aortic dissection (ATAAD) is a complex and emergent cardiovascular surgery that is associated with high perioperative morbidity and mortality. Each cannulation strategy has different benefits and drawbacks during cardiopulmonary bypass. Using a retrospective study design, we aimed to clarify the safety and efficacy of right axillary artery cannulation in combination with femoral artery cannulation compared to single arterial cannulation for ATAAD repair. Methods: From January 2007 to July 2017, 476 adult patients underwent ATAAD repair at a single institution. Patients were classified into groups according to their cannulation strategy: the double arterial cannulation (DAC) group (n = 377; 79.2%) or single arterial cannulation (SAC) group (n = 99; 20.8%). Preoperative demographics, surgical information, and postoperative recovery were compared between both groups. Survival and freedom from reoperation rates were analyzed using the Kaplan-Meier actuarial method. Results: Demographics, comorbidities, and surgical procedures were generally homogenous between the two groups, except for sex, age, and rate of extensive aortic repair. Patients who underwent DAC had lower in-hospital mortality (13.5% vs. 25.3%; P = 0.005) and lower incidence of malperfusion-related complications (18.8% vs. 30.3%; P = 0.011) than those who underwent SAC. During multivariate analysis, SAC was identified as an in-hospital mortality predictor (odds ratio, 2.81; 95% confidence interval, 1.52–5.17; P = 0.001), as were preoperative ventilator support, intraoperative extracorporeal membrane oxygenation installation, and postoperative malperfusion-related complications. Three-year cumulative survival and freedom from reoperation rates were 74.8% and 85.3% for the DAC group and 62.6% and 81.1% for the SAC group, respectively (P = 0.010 and 0.430, respectively). Conclusions: With acceptable short- and mid-term outcomes, DAC is effective and safe for establishing cardiopulmonary bypass during ATAAD repair. [ABSTRACT FROM AUTHOR]

Background: PACAP and VIP are closely related neuropeptides with wide distribution and potent effect in the vasculature. We previously reported vasomotor activity in peripheral vasculature of male wild type (WT) and PACAP-deficient (KO) mice. However, female vascular responses are still unexplored. We hypothesized that PACAP-like activity is maintained in female PACAP KO mice and the mechanism through which it is regulated differs from that of male PACAP KO animals. Methods: We investigated the vasomotor effects of VIP and PACAP isoforms and their selective blockers in WT and PACAP KO female mice in carotid and femoral arteries. The expression and level of different PACAP receptors in the vessels were measured by RT-PCR and Western blot. Results: In both carotid and femoral arteries of WT mice, PACAP1-38, PACAP1-27 or VIP induced relaxation, without pronounced differences between them. Reduced relaxation was recorded only in the carotid arteries of KO mice as compared to their WT controls. The specific VPAC1R antagonist completely blocked the PACAP/VIP-induced relaxation in both arteries of all mice, while PAC1R antagonist affected relaxation only in their femoral arteries. Conclusion: In female WT mice, VPAC1 receptors appear to play a dominant role in PACAP-induced vasorelaxation both in carotid and in femoral arteries. In the PACAP KO group PAC1R activation exerts vasorelaxation in the femoral arteries but in carotid arteries there is no significant effect of the activation of this receptor. In the background of this regional difference, decreased PAC1R and increased VPAC1R availability in the carotid arteries was found. [ABSTRACT FROM AUTHOR]

Media sclerosis (MS) and peripheral artery disease (PAD) may coincide, particularly in type 2 diabetics (T2D) and in patients with chronic kidney disease (CKD). In contrast to non-diabetics, in T2D PAD is more severe and more distal. Although MS is suspected to play a role, the underlying pathophysiological reasons for the differences still remain elusive today. We tested the hypothesis that MS is a promoter of atherosclerosis as it occurs in T2D with PAD by interfering with arterial remodeling using an in-silico simulation. We confirmed that MS aggravates PAD by promoting negative remodeling. We found that the effect is more pronounced in smaller distal arteries compared to larger proximal ones. Our results suggest that the degree of this divergence depends on the ratio between the thickness of the intima relative to the thickness of the media/adventitia of the individually affected arteries. [ABSTRACT FROM AUTHOR]

Background: Limiting the contrast volume to creatinine clearance (V/CrCl) ratio is crucial for preventing contrast-induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI). However, the incidence of CI-AKI and the distribution of V/CrCl ratios may vary according to patient body habitus. Objective: We aimed to identify the clinical factors predicting CI-AKI in patients with different body mass indexes (BMIs). Methods: We evaluated 8782 consecutive patients undergoing PCI and who were registered in a large Japanese database. CI-AKI was defined as an absolute serum creatinine increase of 0.3 mg/dL or a relative increase of 50%. The effect of the V/CrCl ratio relative to CI-AKI incidence was evaluated within the low- (≤25 kg/m2) and high- (>25 kg/m2) BMI groups, with a V/CrCl ratio > 3 considered to be a risk factor for CI-AKI. Results: A V/CrCl ratio > 3 was predictive of CI-AKI, regardless of BMI (low-BMI group: odds ratio [OR], 1.77 [1.42–2.21]; P < 0.001; high-BMI group: OR, 1.67 [1.22–2.29]; P = 0.001). The relationship between BMI and CI-AKI followed a reverse J-curve relationship, although baseline renal dysfunction (creatinine clearance <60 mL/min, 46.9% vs. 21.5%) and V/CrCl ratio > 3 (37.3% vs. 20.4%) were predominant in the low-BMI group. Indeed, low BMI was a significant predictor of a V/CrCl ratio > 3 (OR per unit decrease in BMI, 1.08 [1.05–1.10]; P < 0.001). Conclusions: A V/CrCl ratio > 3 was strongly associated with the occurrence of CI-AKI. Importantly, we also identified a tendency for physicians to use higher V/CrCl ratios in lean patients. Thus, recognizing this trend may provide a therapeutic target for reducing the incidence of CI-AKI. [ABSTRACT FROM AUTHOR]

Introduction: Morphological characterization of leg arteries is of significant importance to detect vascular remodeling triggered by atherosclerotic changes. We determined reference values of vessel diameters and assessed prevalence of stenosis and arterial variations of the lower limb arteries in a healthy male population sample. Methods: Gadolinium-enhanced magnetic resonance angiography at 1.5 Tesla was performed in 756 male participants (median age = 52 years, range = 21–82 years) of the population-based Study of Health in Pomerania. Vessel diameters were measured in 9 predefined segments of the pelvic and leg arteries and 95th percentiles were used for upper reference values of means of left and right side arteries. Results: Reference values of vascular diameters decreased from proximal to distal arteries: common iliac = 1.18cm; internal iliac = 0.75cm; external iliac = 1.03cm; proximal femoral = 1.02cm; distal femoral = 0.77cm; popliteal = 0.69cm; anterior tibial = 0.42cm; posterior tibial = 0.38cm; fibular = 0.40cm. Body-surface area indexed reference values increased with age in all segments. A number of 53 subjects (7.0%) had at least one stenosis, mainly in the lower leg arteries anterior tibial (n = 28, 3.7%), posterior tibial (n = 18, 2.4%) and fibular (n = 20, 2.6%). The risk of stenosis increased considerably with age (odds ratio = 1.08; p<0.001). The most common arterial variant was type I-A in both legs (n = 620, 82%). Conclusion: We present reference values for different pelvic and leg artery segment diameters in men that decrease from proximal to distal and increase with age. Stenoses were most prevalent in lower leg arteries and type I-A was the most common variant in the lower leg. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is an independent risk factor for the development of cardiovascular diseases. Aim of this present study was to evaluate and extend recent research on the influence of obstructive sleep apnea on vascular strain. Methods: A total number of 98 patients were integrated in the study. Patients were grouped according to the Apnea-Hypopnea-Index (AHI) in patients with mild-to-moderate OSA (5/h ≤ AHI < 30/h), severe OSA (AHI ≥ 30/h) and controls (AHI < 5/h). Groups were matched in age, body-mass-index and cardiovascular risks. Vascular strain of common carotid arteries was assessed by ultrasound speckle-tracking. A minor group of 30 patients and controls further underwent assessment of vascular strain of brachial and femoral arteries. Additionally, all patients underwent blood testing to reveal potential influences of inflammatory markers on arterial stiffness. In additional analysis we examined the effect of statin therapy on vascular strain. Results: Patients with OSA showed significantly reduced values of vascular strain of common carotid arteries. Radial and circumferential strains were significantly lower in both patients with mild-to-moderate (p = .05) and patients with severe OSA (p = .001) compared to control. Vascular strain parameters of brachial and femoral arteries showed no consistent results. There were no significant correlations of inflammatory markers with vascular strain parameters. No significant differences in vascular strain were detected between statin and non-statin groups. Conclusion: Patients with OSA show significantly reduced vascular strain assessed by ultrasound-based speckle-tracking. Vascular stiffness increases with the severity of the disease. Target vessels to assess vascular strain in patients with OSA are common carotid arteries, whereas other sites of the arterial tree are not reliable. No significant impact of current statin therapy on vascular strain was found. Further studies are needed to evaluate potential benefit of statins in secondary prevention of atherosclerosis in OSA. [ABSTRACT FROM AUTHOR]

Previous reports indicate roles for acid-sensing ion channels (ASICs) in both peripheral and central chemoreception, but the contributions of ASICs to ventilatory drive in conscious, unrestrained animals remain largely unknown. We tested the hypotheses that ASICs contribute to hypoxic- and hypercapnic-ventilatory responses. Blood samples taken from conscious, unrestrained mice chronically instrumented with femoral artery catheters were used to assess arterial O2, CO2, and pH levels during exposure to inspired gas mixtures designed to cause isocapnic hypoxemia or hypercapnia. Whole-body plethysmography was used to monitor ventilatory parameters in conscious, unrestrained ASIC1, ASIC2, or ASIC3 knockout (-/-) and wild-type (WT) mice at baseline, during isocapnic hypoxemia and during hypercapnia. Hypercapnia increased respiratory frequency, tidal volume, and minute ventilation in all groups of mice, but there were no differences between ASIC1-/-, ASIC2-/-, or ASIC3-/- and WT. Isocapnic hypoxemia also increased respiratory frequency, tidal volume, and minute ventilation in all groups of mice. Minute ventilation in ASIC2-/- mice during isocapnic hypoxemia was significantly lower compared to WT, but there were no differences in the responses to isocapnic hypoxemia between ASIC1-/- or ASIC3-/- compared to WT. Surprisingly, these findings show that loss of individual ASIC subunits does not substantially alter hypercapnic or hypoxic ventilatory responses. [ABSTRACT FROM AUTHOR]

Vascular calcification is a strong and independent predictive factor for cardiovascular complications and mortality. Our previous work identified important discrepancies in plaque composition and calcification types between carotid and femoral arteries. The objective of this study is to further characterize and understand the heterogeneity in vascular calcification among vascular beds, and to identify molecular mechanisms underlying this process. We established ECLAGEN biocollection that encompasses human atherosclerotic lesions and healthy arteries from different locations (abdominal, thoracic aorta, carotid, femoral, and infrapopliteal arteries) for histological, cell isolation, and transcriptomic analysis. Our results show that lesion composition differs between these locations. Femoral arteries are the most calcified arteries overall. They develop denser calcifications (sheet-like, nodule), and are highly susceptible to osteoid metaplasia. These discrepancies may derive from intrinsic differences between SMCs originating from these locations, as microarray analysis showed specific transcriptomic profiles between primary SMCs isolated from each arterial bed. These molecular differences translated into functional disparities. SMC from femoral arteries showed the highest propensity to mineralize due to an increase in basal TGFβ signaling. Our results suggest that biological heterogeneity of resident vascular cells between arterial beds, reflected by our transcriptomic analysis, is critical in understanding plaque biology and calcification, and may have strong implications in vascular therapeutic approaches. [ABSTRACT FROM AUTHOR]

Objective: Genetic P300/CBP-associated factor (PCAF) variation affects restenosis-risk in patients. PCAF has lysine acetyltransferase activity and promotes nuclear factor kappa-beta (NFκB)-mediated inflammation, which drives post-interventional intimal hyperplasia development. We studied the contributing role of PCAF in post-interventional intimal hyperplasia. Methods and results: PCAF contribution to inflammation and intimal hyperplasia was assessed in leukocytes, macrophages and vascular smooth muscle cells (vSMCs) in vitro and in a mouse model for intimal hyperplasia, in which a cuff is placed around the femoral artery. PCAF deficiency downregulate CCL2, IL-6 and TNF-alpha expression, as demonstrated on cultured vSMCs, leukocytes and macrophages. PCAF KO mice showed a 71.8% reduction of vSMC-rich intimal hyperplasia, a 73.4% reduction of intima/media ratio and a 63.7% reduction of luminal stenosis after femoral artery cuff placement compared to wild type (WT) mice. The association of PCAF and vascular inflammation was further investigated using the potent natural PCAF inhibitor garcinol. Garcinol treatment reduced CCL2 and TNF-alpha expression, as demonstrated on cultured vSMCs and leukocytes. To assess the effect of garcinol treatment on vascular inflammation we used hypercholesterolemic ApoE*3-Leiden mice. After cuff placement, garcinol treatment resulted in reduced arterial leukocyte and macrophage adherence and infiltration after three days compared to untreated animals. Conclusions: These results identify a vital role for the lysine acetyltransferase PCAF in the regulation of local inflammation after arterial injury and likely the subsequent vSMC proliferation, responsible for intimal hyperplasia. [ABSTRACT FROM AUTHOR]

Background: The novel nonsteroidal mineralocorticoid receptor (MR) antagonist finerenone holds promise to be safe and efficient in the treatment of patients with heart failure and/or chronic kidney disease. However, its effects on vascular function remain elusive. Purpose: The aim of this study was to determine the functional effect of selective MR antagonism by finerenone in vascular cells in vitro and the effect on vascular remodeling following acute vascular injury in vivo. Methods and results: In vitro, finerenone dose-dependently reduced aldosterone-induced smooth muscle cell (SMC) proliferation, as quantified by BrdU incorporation, and prevented aldosterone-induced endothelial cell (EC) apoptosis, as measured with a flow cytometry based caspase 3/7 activity assay. In vivo, oral application of finerenone resulted in an accelerated re-endothelialization 3 days following electric injury of the murine carotid artery. Furthermore, finerenone treatment inhibited intimal and medial cell proliferation following wire-induced injury of the murine femoral artery 10 days following injury and attenuated neointimal lesion formation 21 days following injury. Conclusion: Finerenone significantly reduces apoptosis of ECs and simultaneously attenuates SMC proliferation, resulting in accelerated endothelial healing and reduced neointima formation of the injured vessels. Thus, finerenone appears to provide favorable vascular effects through restoring vascular integrity and preventing adverse vascular remodeling. [ABSTRACT FROM AUTHOR]

Objective: Evaluation of the impact of the sheath diameter on vascular complications and mortality in transfemoral aortic valve implantation. Method: Between 2012 and 2014, 183 patients underwent the procedure using a sheath diameter of 18–24 F. This collective was divided into two groups: group 1, with a sheath diameter of 18F (G1, n = 94), consisted of patients with 18F Medtronic Sentrant and 18 F Direct Flow sheaths, and group 2 with a sheath diameter of 19–24 F (G2, n = 89) consisted of patients with Edwards expandable e-sheath and Solopath sheaths. Perclose-Proglide® was used as a closure device in all patients. Results: G1 had significantly more female patients (64.9% vs. 46.1% in G2, p = 0.01) and the average BMI was lower (26 ± 4.5% vs. 27.4 ± 4.7%, p = 0.03). There was no significant difference in the incidence of major and minor vascular complications (G1: 12.8% vs. G2: 12.4%, p = 0.9). 30-day mortality was similar in both groups (G1: 6.4 ± 2.5% [95% CI: 0.88–0.98], G2: 3.7 ± 1.9% [95% CI: 0.92–0.99]. The Kaplan Meier analysis of survival revealed no significant differences either. Conclusion: The difference in sheath diameter had no effect on either incidence or severity of vascular complications. There was no impact on mortality either. [ABSTRACT FROM AUTHOR]

Purpose: The risk of complications associated with femoral venous catheterization could be potentially reduced if the procedure was performed at the location where the cross-sectional area (CSA) of the vessel is the largest. The diameter of the femoral vein depends on leg position as well as the distance from the inguinal ligament. We determined the CSA of the right femoral vein in three different leg positions at two distances from the inguinal ligament. Subjects and methods: Informed consent was given by 205 healthy volunteers aged 19–39 years, mean: 23±3 years (108 women, 97 men). Ultrasonographic examinations were performed using a linear 14-MHz transducer with CSA measurements in three leg positions: abduction, abduction+external rotation, abduction+external rotation+90° knee flexion/frog-leg position; at levels 20 mm caudally to the inguinal ligament, and 20 mm caudally to the inguinal crease. Results: We found significant differences in mean values of CSA in three leg positions regardless of the measurement level. The largest mean CSA (114 mm2±35 mm2) was found at the proximal level in the frog-leg position. There was a significant association of the CSA with sex and height. The CSA in males was greater than in females in all leg positions at the level of 20 mm caudally to the inguinal crease, while 20 mm caudally to the inguinal ligament the CSA was larger in females. The CSA of 25% of the femoral vein was smaller than 45.0 mm2 at the proximal level, and 31.5 mm2 at the distal level, which refers to diameters of 5.3 mm, and 4.5 mm, respectively. Conclusions: The cross-sectional area of the femoral vein is the largest in the frog-leg position, and depends on gender. [ABSTRACT FROM AUTHOR]

Hospitalized patients often receive oxygen supplementation, which can lead to a supraphysiological oxygen tension (hyperoxia). Hyperoxia can have hemodynamic effects, including an increase in systemic vascular resistance. This increase suggests hyperoxia-induced vasoconstriction, yet reported direct effects of hyperoxia on vessel tone have been inconsistent. Furthermore, hyperoxia-induced changes in vessel diameter have not been studied in mice, currently the most used mammal model of disease. In this study we set out to develop a pressure-myograph model using isolated vessels from mice for investigation of pathways involved in hyperoxic vasoconstriction. Isolated conduit and resistance arteries (femoral artery and gracilis arteriole, respectively) from C57BL/6 mice were exposed to normoxia (PO2 of 80 mmHg) and three levels of hyperoxia (PO2 of 215, 375 and 665 mmHg) in a no-flow pressure myograph setup. Under the different PO2 levels, dose-response agonist induced endothelium-dependent vasodilation (acetylcholine, arachidonic acid), endothelium-independent vasodilation (s-nitroprusside), as well as vasoconstriction (norepinephrine, prostaglandin F2α) were examined. The investigated arteries did not respond to oxygen by a change in vascular tone. In the dose-response studies, maximal responses and EC50 values to any of the aforementioned agonists were not affected by hyperoxia either. We conclude that arteries and arterioles from healthy mice are not intrinsically sensitive to hyperoxic conditions. The present ex-vivo model is therefore not suitable for further research into mechanisms of hyperoxic vasoconstriction. [ABSTRACT FROM AUTHOR]

Combined estrogen-progestin preparations (CEPs) are associated with thromboembolic (TE) side effects. The aim of this study was to evaluate the incidence of TE using the Japanese Adverse Drug Event Report (JADER) database. Adverse events recorded from April 2004 to November 2014 in the JADER database were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website (). We calculated the reporting odds ratios (RORs) of suspected CEPs, analyzed the time-to-onset profile, and assessed the hazard type using Weibull shape parameter (WSP). Furthermore, we used the applied association rule mining technique to discover undetected relationships such as the possible risk factors. The total number of reported cases in the JADER contained was 338,224. The RORs (95% confidential interval, CI) of drospirenone combined with ethinyl estradiol (EE, Dro-EE), norethisterone with EE (Ne-EE), levonorgestrel with EE (Lev-EE), desogestrel with EE (Des-EE), and norgestrel with EE (Nor-EE) were 56.2 (44.3–71.4), 29.1 (23.5–35.9), 42.9 (32.3–57.0), 44.7 (32.7–61.1), and 38.6 (26.3–56.7), respectively. The medians (25%–75%) of the time-to-onset of Dro-EE, Ne-EE, Lev-EE, Des-EE, and Nor-EE were 150.0 (75.3–314.0), 128.0 (27.0–279.0), 204.0 (44.0–660.0), 142.0 (41.3–344.0), and 16.5 (8.8–32.0) days, respectively. The 95% CIs of the WSP-β for Ne-EE, Lev-EE, and Nor-EE were lower and excluded 1. Association rule mining indicated that patients with anemia had a potential risk of developing a TE when using CEPs. Our results suggest that it is important to monitor patients administered CEP for TE. Careful observation is recommended, especially for those using Nor-EE, and this information may be useful for efficient therapeutic planning. [ABSTRACT FROM AUTHOR]

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional neuropeptide in the VIP/secretin/glucagon peptide superfamily. Two active forms, PACAP1-38 and PACAP1-27, act through G proteincoupled receptors, the PAC1 and VPAC1/2 receptors. Effects of PACAP include potent vasomotor activity. Vasomotor activity and organ-specific vasomotor effects of PACAP-deficient mice have not yet been investigated; thus, the assessment of its physiological importance in vasomotor functions is still missing. We hypothesized that backup mechanisms exist to maintain PACAP pathway activity in PACAP knockout (KO) mice. Thus, we investigated the vasomotor effects of exogenous vasoactive intestinal peptide (VIP) and PACAP polypeptides in PACAP wild-type (WT) and PACAP-deficient (KO) male mice. Methods: Carotid and femoral arteries were isolated from 8-to 12-week-old male WT and PACAP-KO mice. Vasomotor responses were measured with isometric myography. Results: In the arteries of WT mice the peptides induced relaxations, which were significantly greater to PACAP1-38 than to PACAP1-27 and VIP. In KO mice, PACAP1-38 did not elicit relaxation, whereas PACAP1-27 and VIP elicited significantly greater relaxation in KO mice than in WT mice. The specific PAC1R and VPAC1R antagonist completely blocked the PACAP-induced relaxations. Conclusion: Our data suggest that in PACAP deficiency, backup mechanisms maintain arterial relaxations to polypeptides, indicating an important physiological role for the PACAP pathway in the regulation of vascular tone. [ABSTRACT FROM AUTHOR]

The de-differentiation and proliferation of smooth muscle cells (SMCs) are widely accepted as the major contributor to vascular remodeling. However, recent studies indicate that vascular stem cells (VSCs) also play an important role, but their relative contribution remains to be elucidated. In this study, we used genetic lineage tracing approach to further investigate the contribution of SMCs and VSCs to neointimal thickening in response to endothelium denudation injury or artery ligation. In vitro and in vivo analysis of MYH11-cre/Rosa-loxP-RFP mouse artery showed that SMCs proliferated at a much slower rate than non-SMCs. Upon denudation or ligation injury, two distinct types of neointima were identified: Type-I neointimal cells mainly involved SMCs, while Type II mainly involved non-SMCs. Using Sox10-cre/Rosa-loxP-LacZ mice, we found that Sox10+ cells were one of the cell sources in neointima. In addition, lineage tracing using Tie2-cre/Rosa-LoxP-RFP showed that endothelial cells also contributed to the neointimal formation, but rarely transdifferentiated into mesenchymal lineages. These results provide a novel insight into the contribution of vascular cells to neointima formation, and have significant impact on the development of more effective therapies that target specific vascular cell types. [ABSTRACT FROM AUTHOR]

Although the clinical range of interventions for coronary arteries is about 2 to 5 mm, the range of diameters of peripheral vasculature is significantly larger (about 10 mm for human iliac artery). When the vessel diameter is increased, the spacing between excitation electrodes on a conductance sizing device must also increase to accommodate the greater range of vessel diameters. The increase in the excitation electrodes distance, however, causes higher parallel conductance or current losses outside of artery lumen. We have previously shown that the conductance catheter/guidewire excitation electrode distances affects the measurement accuracy for the peripheral artery lumen sizing. Here, we propose a simple solution that varies the detection electrode distances to compensate for parallel conductance losses. Computational models were constructed to simulate the conductance guidewire with various electrodes spacing combinations over a range of peripheral artery lumen diameters and surrounding tissue electrical conductivities. The results demonstrate that the measurement accuracy may be significantly improved by increased detection spacing. Specifically, an optimally configured detection/excitation spacing (i.e., 5-5-5 or an equidistant electrode interval with a detection-to-excitation spacing ratio of 0.3) was shown to accurately predict the lumen diameter (i.e., -10% < error < 10%) over a broad range of peripheral artery dimensions (4 mm < diameter < 10 mm). The computational results were substantiated with both ex-vivo and in-vivo measurements of peripheral arteries. The present results support the accuracy of the conductance technique for measurement of peripheral reference vessel diameter. [ABSTRACT FROM AUTHOR]

This paper aims to study the thrombolytic effect of low-frequency ultrasound combined with targeted urokinase-containing microbubble contrast agents on treatment of thrombosis in rabbit femoral artery; and to determine the optimal combination of parameters for achieving thrombolysis in this model. A biotinylated-avidin method was used to prepare microbubble contrast agents carrying urokinase and Arg-Gly-Asp-Ser (RGDS) peptides. Following femoral artery thrombosis in New Zealand white rabbits, microbubble contrast agents were injected intravenously, and ultrasonic exposure was applied. A 3 × 2 × 2 factorial table was applied to categorize the experimental animals based on different levels of combination of ultrasonic frequencies (Factor A: 1.6 MHz, 2.2 MHz, 2.8 MHz), doses of urokinase (Factor B: 90,000 IU/Kg, 180,000 IU/Kg) and ultrasound exposure time (Factor C: 30 min, 60 min). A total of 72 experimental animals were randomly divided into 12 groups (n = 6/group). Doppler techniques were used to assess blood flow in the distal end of the thrombotic femoral artery during the 120 minutes thrombolysis experiment. The rate of recanalization following thrombolysis was calculated, and thrombolytic efficacy was evaluated and compared. The thrombolytic recanalization rate for all experimental subjects after thrombolytic therapy was 68.1%. The optimal parameters for thrombolysis were determined to be 1) an ultrasound frequency of 2.2 MHz and 2) a 90,000 IU/kg dose of urokinase. Ultrasound exposure time (30 min vs. 60 min) had no significant effect on the thrombolytic effects. The combination of local low-frequency ultrasound radiation, targeted microbubbles, and thrombolytic urokinase induced thrombolysis of femoral artery thrombosis in a rabbit model. The ultrasonic frequency of 2.2 MHz and urokinase dose of 90,000 IU/kg induced optimal thrombolytic effects, while the application of either 30 min or 60 min of ultrasound exposure had similar effects. [ABSTRACT FROM AUTHOR]

Viscolin, an extract of Viscum coloratum, has anti-inflammatory and anti-proliferative properties against harmful stimuli. The aim of the study was to examine the anti-proliferative effects of viscolin on platelet derived growth factor-BB (PDGF)-treated human aortic smooth muscle cells (HASMCs) and identify the underlying mechanism responsible for these effects. Viscolin reduced the PDGF-BB-induced HASMC proliferation and migration in vitro; it also arrested HASMCs in the G0/G1 phase by decreasing the protein expression of Cyclin D1, CDK2, Cyclin E, CDK4, and p21Cip1 as detected by Western blot analysis. These effects may be mediated by reduced PDGF-induced phosphorylation of ERK1/2, JNK, and P38, but not AKT as well as inhibition of PDGF-mediated nuclear factor (NF)-κB p65 and activator protein 1 (AP-1)/c-fos activation. Furthermore, viscolin pre-treatment significantly reduced neointimal hyperplasia of an endothelial-denuded femoral artery in vivo. Taken together, viscolin attenuated PDGF–BB-induced HASMC proliferation in vitro and reduced neointimal hyperplasia in vivo. Thus, viscolin may represent a therapeutic candidate for the prevention and treatment of vascular proliferative diseases. [ABSTRACT FROM AUTHOR]

Minipigs are frequently used in (neuro-)interventional research. Longitudinal experiments may require repeated vessel access via the femoral artery. Anticoagulation and incompliance of the animals necessitates the use of a vascular closure device (VCD). The effects of the Angio-Seal VCD in minipigs were longitudinally assessed. Minipig (42±8.4 kg body weight) femoral arteries were sealed using the 8F (n = 6) or 6F (n = 7) Angio-Seal VCD. The pre-interventional femoral artery diameter was 5.1±0.4 mm (4.3–5.8 mm). Sealed puncture sites were analysed angiographically as well as by computed tomography angiography (CTA) for a mean period of 14.1±8.0 weeks (1–22 weeks). All animals were constantly treated with acetylsalicylic acid (ASS) (450 mg/d (n = 7) or 100 mg/d (n = 1)) and clopidogrel (75 mg/d (n = 8)). Non-instrumented (n = 2) and arteries sealed using the VCD (n = 2) were examined histologically. No postoperative hemorrhagic complications were observed. Three arteries were occluded after VCD placement (1 animal diagnosed after 4 weeks (8F), 2 animals after 1 week (6F)) and remained so until the end of the experiments after 22, 12 and 4 weeks, respectively. In one artery a 50% stenosis 8 weeks after application of a 6F Angio-Seal was detected. In 69.2% (n = 9) the VCD was applied without complications. Histopathological analysis of the sealed arterial segments showed subtotal obliteration of the vessel lumen, formation of collagenous tissue and partial damage of the internal elastic lamina. The Angio-Seal VCD prevents relevant hemorrhagic complications in minipigs treated with dual platelet inhibition, but is associated with increased vessel occlusion rates. [ABSTRACT FROM AUTHOR]

Leptomeningeal anastomoses play a critical role in regulating vascular re-perfusion following obstruction, however, the mechanisms regulating their development remains under investingation. Our current findings indicate that EphA4 receptor is a novel negative regulator of collaterogenesis. We demonstrate that EphA4 is highly expressed on pial arteriole collaterals at post-natal day (P) 1 and 7, then significantly reduced by P21. Endothelial cell (EC)-specific loss of EphA4, EphA4f/f/Tie2::Cre (KO), resulted in an increase in the density but not diameter of pial collaterals compared to WT mice. ECs isolated from KO mice displayed a 3-fold increase in proliferation, enhanced migration, tube formation and elevated levels of phospho(p)-Akt compared to WT ECs. Attenuating p-Akt, using LY294002, reduced the proliferative and migration effects in the KO ECs. RNAseq analysis also revealed altered expression patterns for genes that regulate cell proliferation, vascular development, extracellular matrix and immune-mediate responses, namely MCP-1, MMP2 and angiopoietin-1. Lastly, we show that induction of hindlimb ischemia resulted in accelerated re-perfusion, collateral remodeling and reduced tissue necrosis in the absence of EC-specific EphA4 compared to WT mice. These findings demonstrate a novel role for EphA4 in the early development of the pial collateral network and suggests a role in regulating vascular remodeling after obstruction. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of type 2 diabetes is increasing rapidly in the young population. The clinical characteristics and risk factors for young type 2 diabetes patients with atherosclerosis are not fully explicated. The aim of the present study was to investigate various clinical and biochemical characteristics of young type 2 diabetic patients with atherosclerosis. Design and Methods: This was a cross-sectional study. The study involved 2199 hospitalized patients with type 2 diabetes. The young patients were classified into the atherosclerotic group or the non-atherosclerotic group, and we also enrolled an older group with peripheral atherosclerosis disease and an age of at least 45 years. Comparisons were made between the different groups to investigate the cardiovascular and metabolic risk profiles of young type 2 diabetes patients with atherosclerosis. We also used logistic regression models to assess the atherosclerosis risk factors for young patients. Results: Compared to older type 2 diabetes patients with atherosclerosis, young patients with atherosclerosis had more deleterious profiles of weight and hyperlipidemia. Only age and diabetes duration were found to be significant independent risk factors for atherosclerosis in young patients. The ratio of the presence of atherosclerosis in the lower extremity arteries alone was significantly higher in young patients than older patients (26.4% vs. 14.0%, P = 0.000). Conclusion: Young type 2 diabetes patients with atherosclerosis have more adverse cardiovascular risk profiles and inadequate control of these risk factors. Lower extremity examination is of high importance in young patients. [ABSTRACT FROM AUTHOR]

Aims: Multiple factors regulate arteriogenesis. Peripheral nerves play a crucial role in vascular remodeling, but the function of peripheral nerves during arteriogenesis is obscure. Our study investigated the contribution of denervation to arteriogenesis during post-ischemic recovery from hindlimb femoral artery ligation. Methods and Results: Sprague-Dawley rats were randomly allocated into four groups of normal control (NC), hindlimb ischemia (HI), hindlimb ischemia with denervation (HID) and hindlimb simple denervation (HD). Hindlimb ischemic recovery was assessed by clinical assessment and tibialis anterior muscle remodeling on day 28 post-surgery. Blood flow was determined by laser Doppler imaging on day 0, 3, 7, 14 and 28 post-surgery. Collateral number of hindlimb was observed by angiography and gracilis muscles were tested by immunostaining on day 7 and 28 post-surgery. Angiogenesis was accessed by counting CD31 positive capillaries in tibialis anterior muscles on day 28 post-surgery. Group HID showed impaired ischemic recovery compared with the other 3 groups and impaired blood flow recovery compared with group HI on day 28 post-surgery. The collateral number and capillary density of group HID were lower than group HI. The collateral diameter of both group HID and group HI significantly increased compared with group NC. However, the lumen diameter was much narrower and the vessel wall was much thicker in group HID than group HI. We also demonstrated that the thickened neointima of collaterals in group HID comprised of smooth muscle cells and endothelial cells. Conclusions: Denervation of the ligated femoral artery in the hindlimb impairs ischemic recovery via impaired perfusion. The possible mechanisms of impaired perfusion are lower collateral number, lower capillary density and most likely narrower lumen, which damage ischemic recovery. This study illustrates the crucial role of peripheral nerves in arteriogenesis using a model combined ischemia with denervation in hindlimb. [ABSTRACT FROM AUTHOR]

Aims: Studies in global androgen receptor knockout (G-ARKO) and orchidectomised mice suggest that androgen accelerates reperfusion of the ischaemic hindlimb by stimulating angiogenesis. This investigation used novel, vascular cell-specific ARKO mice to address the hypothesis that the impaired hindlimb reperfusion in G-ARKO mice was due to loss of AR from cells in the vascular wall. Methods and Results: Mice with selective deletion of AR (ARKO) from vascular smooth muscle cells (SM-ARKO), endothelial cells (VE-ARKO), or both (SM/VE-ARKO) were compared with wild type (WT) controls. Hindlimb ischaemia was induced in these mice by ligation and removal of the femoral artery. Post-operative reperfusion was reduced in SM-ARKO and SM/VE-ARKO mice. Immunohistochemistry indicated that this was accompanied by a reduced density of smooth muscle actin-positive vessels but no change in the density of isolectin B4-positive vessels in the gastrocnemius muscle. Deletion of AR from the endothelium (VE-ARKO) did not alter post-operative reperfusion or vessel density. In an ex vivo (aortic ring culture) model of angiogenesis, AR was not detected in vascular outgrowths and angiogenesis was not altered by vascular ARKO or by exposure to dihydrotestosterone (DHT 10−10–10-7M; 6 days). Conclusion: These results suggest that loss of AR from vascular smooth muscle, but not from the endothelium, contributes to impaired reperfusion in the ischaemic hindlimb of G-ARKO. Impaired reperfusion was associated with reduced collateral formation rather than reduced angiogenesis. [ABSTRACT FROM AUTHOR]

Signalling pathways underlying the phenomenon of remote ischaemic preconditioning (RPc) cardioprotection are not completely understood. The existing evidence agrees that intact sensory innervation of the remote tissue/organ is required for the release into the systemic circulation of preconditioning factor(s) capable of protecting a transplanted or isolated heart. However, the source and molecular identities of these factors remain unknown. Since the efficacy of RPc cardioprotection is critically dependent upon vagal activity and muscarinic mechanisms, we hypothesized that the humoral RPc factor is produced by the internal organ(s), which receive rich parasympathetic innervation. In a rat model of myocardial ischaemia/reperfusion injury we determined the efficacy of limb RPc in establishing cardioprotection after denervation of various visceral organs by sectioning celiac, hepatic, anterior and posterior gastric branches of the vagus nerve. Electrical stimulation was applied to individually sectioned branches to determine whether enhanced vagal input to a particular target area is sufficient to establish cardioprotection. It was found that RPc cardioprotection is abolished in conditions of either total subdiaphragmatic vagotomy, gastric vagotomy or sectioning of the posterior gastric branch. The efficacy of RPc cardioprotection was preserved when hepatic, celiac or anterior gastric vagal branches were cut. In the absence of remote ischaemia/reperfusion, electrical stimulation of the posterior gastric branch reduced infarct size, mimicking the effect of RPc. These data suggest that the circulating factor (or factors) of RPc are produced and released into the systemic circulation by the visceral organ(s) innervated by the posterior gastric branch of the vagus nerve. [ABSTRACT FROM AUTHOR]

Aim Further to its pivotal role in haemostasis, factor Xa ( FXa) promotes effects on the vascular wall. The purpose of the study was to evaluate if FXa modifies the expression level of energy metabolism and oxidative stress-related proteins in femoral arteries obtained from type 2 diabetic patients with end-stage vasculopathy. Methods Femoral arteries were obtained from 12 type 2 diabetic patients who underwent leg amputation. Segments from the femoral arteries were incubated in vitro alone and in the presence of 25 nmol l−1 FXa and 25 nmol l−1 FXa + 50 nmol l−1 rivaroxaban. Results In the femoral arteries, FXa increased triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase isotype 1 expression but decreased pyruvate dehydrogenase expression. These facts were accompanied by an increased content of acetyl- CoA. Aconitase activity was reduced in FXa-incubated femoral arteries as compared with control. Moreover, FXa increased the protein expression level of oxidative stress-related proteins which was accompanied by an increased malonyldialdehyde arterial content. The FXa inhibitor, rivaroxaban, failed to prevent the reduced expression of pyruvate dehydrogenase induced by FXa but reduced acetyl- CoA content and reverted the decreased aconitase activity observed with FXa alone. Rivaroxaban + FXa but not FXa alone increased the expression level of carnitine palmitoyltransferase I and II, two mitochondrial long chain fatty acid transporters. Rivaroxaban also prevented the increased expression of oxidative stress-related proteins induced by FXa alone. Conclusions In femoral isolated arteries from type 2 diabetic patients with end-stage vasculopathy, FXa promoted disruption of the aerobic mitochondrial metabolism. Rivaroxaban prevented such effects and even seemed to favour long chain fatty acid transport into mitochondria. [ABSTRACT FROM AUTHOR]

Clinically revealed, non-uniform distribution of peripheral vascular diseases throughout the arterial tree suggests that haemodynamic forces can modulate the endothelial dysfunction. In the present study the bilateral differences of deep (DFA) and superficial (SFA) femoral artery blood velocity waveform parameters were examined in relation to artery ramification patterns and subject anthropometry. Young, sedentary women (n = 25; age 21.2 ± 3.6 years) were enrolled. Anthropometric data as well as systemic cardiovascular parameters (arterial pressure, heart rate and cardiac output) and Doppler velocity spectrum of SFA and DFA were instantly registered in rest conditions. The study revealed a slight and mutually independent anatomical and morphometric asymmetries of femoral arteries in paired legs which were fluctuation type (do not display any directional tendency). Also bilateral asymmetry of artery haemodynamic parameters was related neither to subjects’ anthropometric nor artery anatomical parameters. The magnitude of haemodynamic asymmetry is larger for retrograde linear velocity, retrograde shear rate and oscillatory index – parameters which reflect peripheral resistance of microcirculatory bed and thus has a rather functional origin. Possibly, the observed unilateral changes of femoral artery haemodynamic parameters of young healthy and sedentary women could be considered as a sign of potential genesis of artery structure pathological changes in older age.