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The authors present a short review of the personality, clinical and scientific contributions of a distinguished member of our Academy, the Artery Society and so many others, where he contributed landmark advances in many fields of arterial function and cardiovascular risk. The Editorial Board of the Artery Research Journal and the Executive Committee of the Artery Society present their due respects to Prof. Michel Safar. [ABSTRACT FROM AUTHOR]

Aims Although the risk of thrombosis is well documented for inflammatory bowel disease [IBD] patients, the underlying pathological mechanism seems to be different from other thrombotic conditions. Determining the factors responsible for the increased risk of thrombosis in IBD would help to improve the management of this frequent complication. Methods We studied the interplay between platelets, coagulation, and von Willebrand factor [VWF] in 193 IBD patients and in experimental models [acute and chronic] of colitis in wild-type and VWF-deficient mice. Results We found a platelet-dependent increase in thrombin generation in IBD patients and in our mouse model of colitis. Agglutinated platelets were present in the blood of patients and mice. Interestingly, we observed not only a significant increase in total VWF antigen, but we were also able to detect the presence of active VWF [VWF in its platelet-binding conformation; 3.2 ± 2.7 μg/mL] in the plasma of 30% of all IBD patients. In healthy controls, active VWF levels were <0.3 μg/mL. This led us to further explore experimental colitis in VWF-deficient mice and we observed that these mice were protected against the procoagulant state triggered by the colitis. Unexpectedly, these mice also showed a significant worsening of colitis severity in both acute and chronic models. Conclusion Platelets and VWF [including its active form] appear to be central players in the procoagulant phenotype in IBD. We observed that the role of VWF in haemostasis differs from its role in colonic tissue healing, potentially opening new therapeutic avenues for a life-threatening complication in IBD patients. [ABSTRACT FROM AUTHOR]

Background: Pulse wave velocity (PWV) is a marker of arterial stiffness, which is intrinsically highly correlated with blood pressure (BP). However, the interplay of PWV and BP heritability has not been extensively studied. This study aimed to estimate the heritability of PWV and BP and determine the genetic correlation between PWV and BP. Methods: The heritability of PWV and BP was estimated in 1080 subjects from the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux) cohort with at least one relative using a linear mixed model within one frequentist and one Bayesian framework implemented, respectively, in the Gaston and MCMCglmm R packages. Then their genetic correlations were also estimated. Results: The heritability estimations for PWV were within the same range of the heritability of systolic BP and diastolic BP (23%, 19%, and 27%, respectively). Daytime heritability of BP was higher than nighttime BP. In addition, phenotypic correlations between PWV and systolic BP/diastolic BP were, respectively, 0.34 and 0.23, whereas nonsignificant genetic correlations were 0.08 and 0.22 respectively, indicating that PWV and diastolic BP shared more polygenic codeterminants than PWV and systolic BP. Conclusions: Our results suggest that the heritability of PWV is >20% and within the same range as BP heritability. It also suggests that the link between PWV and BP goes beyond phenotypic association: PWV and BP (in particular diastolic BP) share common genetic determinants. This genetic interdependence of PWV and BP appears largely polygenic. [ABSTRACT FROM AUTHOR]

In December 2019, an outbreak of pneumonia caused by a novel Coronavirus (COVID-19) spread rapidly worldwide. Although the clinical manifestations of COVID-19 are dominated by respiratory symptoms, the cardiovascular system is extensively affected at multiple levels. Due to the unprecedented consequences of the COVID-19 pandemic, the ARTERY society decided to launch the Covid-19 effects on ARTErial StIffness and vascular AgeiNg (CARTESIAN) study — the first international multicentre study into the effects of COVID-19 on non-invasive biomarkers of vascular ageing. The main study objective is to evaluate the presence of Early Vascular Ageing (EVA) 6 and 12 months after COVID-19 infection. Secondary objectives are to study the effect of COVID-19 disease severity on EVA, to investigate the role of psychosocial factors in COVID-19 induced EVA, and to investigate the potential modifying effect of comorbidities and chronic treatments. In the CARTESIAN study, a broad array of cardiovascular measurements, including carotid-femoral pulse wave velocity, central blood pressure, carotid ultrasound, brachial flow-mediated dilatation, will be performed. To date, 43 centres from 21 countries have agreed to participate, with an expected study population of >2500 individuals. To our knowledge, CARTESIAN will be the first study to provide insight into the relationship between COVID-19, its severity, and early vascular ageing in a large cohort, potentially enabling future care and diagnostics to be more focused on the most vulnerable. [ABSTRACT FROM AUTHOR]

Background: With aging and atherosclerosis plaque development, endothelial permeability increases leading to blood and platelets (PLT) infiltration into the vascular wall. In the media, vascular smoothmuscle cells (VSMCs) are crucial for clearance of infiltrated molecules and cells including senescent red blood cells (1). Moreover, blood has a high concentration of macromolecules making it a macromolecularly crowded environment (MMC). The objective is to decipher the clearance mechanisms of PLT by VSMCs and the influence of MMC on it. Methods: Human VSMCs were cultured with either human: (i) fresh PLT, (ii) ADP-activated PLT, (iii) senescent PLT. PLT and VSMCs were stained with fluorescent tracers prior their co-culture. We also cultured VSMC in media supplemented with crowders to mimic MMC. Results: After three or seven days of co-culture, we observed that activated and/or senescent PLT, which are characterized by phosphatidylserine exposure, were localized within VSMCs. In contrast to fresh red blood cells that are not phagocytosed by VSMCs, fresh PLT were also entrapped within VSMCs. We then stained VSMCs with phalloidin, an actin filament dye, revealing that PLT are surrounded by an actin shell within the VSMC. In addition, we observed that MMC modified the deposition of extracellular matrix (fibronectin, laminin and sugar moieties) by VSMCs. Conclusions: VSMCs engulf PLT with an actin-dependent endocytosis process and MMC modifies the secretory phenotype of VSMC. PLT engulfment could be an inducible pathogenic event that is responsible for VSMC phenotypic switching in atherosclerosis and their procoagulant status. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory bowel disease (IBD) represents an independent risk factor for thrombosis. However, the causes of this increased risk of thrombosis are still elusive. Objectives: We aim to decipher the main players in the procoagulant phenotype associated with IBD.Methods and Results: Coagulation phenotype assessment was performed in IBD patients included in the "I-BANK project" (CHRU Nancy), a prospective monocentric study recruiting 1000 IBD patients and in a mouse model of IBD (dextran sulphate sodium: DSS). We found an increase in platelet count in active IBD patients and an increased thrombin generation (TG) in platelet-rich plasma. Similar results were obtained in mice treated with DSS. In platelet-poor plasma, TG was not increased, highlighting the role of platelets in this phenotype. In addition, both mice and active patients showed platelet agglutination on blood smears. As circulating von Willebrand factor (VWF), which has a procoagulant function and may be involved in platelet agglutination, is elevated in IBD patients, we used VWF-deficient mice. In these mice, TG in platelet-rich plasma was not increased in response to DSS treatment. In contrast, VWF-deficient mice receiving DSS showed worsened colonic tissue damage, highlighting the importance of maintaining a normal coagulation balance in IBD. Conclusion: The procoagulant phenotype in IBD depends on platelet agglutination via VWF. Further studies are needed to assess the possible beneficial effect of VWF inhibition in IBD patients at high risk of thrombosis without aggravating tissue damage. [ABSTRACT FROM AUTHOR]

Background: Integrin av is a receptor for adhesion proteins expressed at high density in vascular smooth muscle cells (VSMC) whose phenotypic modulation plays a crucial role in arterial ageing. Objectives: To define the arterial phenotype in mice conditionally inactivated for the integrin av subunit in VSMC and the role of this integrin in angiotensin II (Ang II)-induced arterial and VSMC stiffness. Methods and Results: We used a VSMC specific knock-out αv mouse model induced in adult mice by injection of tamoxifen. Trangenic mice (αvSMKO) and control littermates (Ctrl) were infused with Ang II (1.5 mg/kg/day) for 4 weeks. The pressure effect of Ang II was similar in Ctrl and αvSMKO mice. The carotid distensibility/pressure and elastic modulus/wall stress curves were similar in control and αvSMKO mice, indicating comparable arterial stiffness. Ang II treatment resulted in increased carotid stiffness in both groups without changes in vascular reactivity and myogenic tone. Electronic microscopy revealed less vesicles containing fiber-like materials in the SMCs of Ang II-treated αvSMKO carotids Elastic modulus of cultured VSMCs determined using atomic force microscopy was higher after Ang II treatment in cells from both groups. At baseline and after treatment, elastic modulus was higher in cells from αvSMKO mice than in cells from Ctrl mice. Conclusion: Inactivation of αv-containing integrins on VSMCs increases cell stiffness. The general mechanism involves a cross-talk between extracellular matrix, αv integrins and cytoskeletal complex. The lack of distensibility changes suggests additional changes at the level of αv-mediated dynamics of focal adhesion. [ABSTRACT FROM AUTHOR]

With advancing age, changes in the arterial wall contribute to what has been called vascular aging, and in some prematurely affected subjects even early vascular aging (EVA).[[1], [2], [3], [4], [5]] Several years ago,[1] we listed various components of EVA, including arteriosclerosis, atherosclerosis, and excess vasoconstriction, with their clinical expression: arterial stiffening and increased central pulse pressure, carotid intima media thickening and endothelial dysfunction, and increased total peripheral resistance, respectively. However, an average vascular aging may not be the desirable goal for patients and their physicians in a population where cardiovascular risk factors are prevalent, and an ideal aging[8] or at least a healthy vascular aging (HVA)[38],[39] would be preferable. The boundaries between early vascular aging (EVA), average vascular aging, healthy vascular aging (HVA), and supernormal vascular aging (SUPERNOVA) are presented as gray zones (Text). Thus, vascular aging based on cardiovascular risk factor may fail at identifying people excessively sensitive (EVA) to or protected against (HVA) risk factors, whereas PWV represents the cumulative damage of all cardiovascular risk factors on the arterial wall. The glucagon-like peptide-1 analog exendin-4 may also contribute to the redox homeostasis by reducing the nucleocytoplasmic shuttling of Nrf2 through its acetylation, thus increasing its transcriptional activity and decreasing VSMC senescence.[68] Localized disturbed blood flow has emerged as a master regulator of the association of Nrf2 with HDAC1/2/3 leading to deacetylation of Nrf2 and sensitizing the endothelium to oxidative stress.[69] Additional potential mechanisms holding off vascular aging and VSMC senescence in NMRs include increased levels of high molecular mass hyaluronan and differentially expressed long noncoding RNAs among which several are coexpressed with HA-related genes.[70]. [Extracted from the article]

The article focuses on the relation between hypertension and arterial stiffness and focuses on the research on Windkessel Model and Aortic Stiffness and the age related changes in the disease.

Introduction: Aneurysms of the ascending (TAA) and the abdominal aorta (AAA) share the common feature of dilation of the aorta but differ by their respective physiopathology and tissue environment in human. AAA is characterized by associated thrombosis forming an intraluminal clot, whereas thrombotic events are extremely rare in TAA, suggesting different coagulant properties between AAA and TAA. Objectives: To compare coagulation capacities at tissue and cellular levels, derived from both AAA and TAA. Methods and Results: Human healthy aorta, AAA or TAA tissues and primary cultures of aortic smooth muscle cells (SMCs) were used. Thrombin generation was monitored by thrombography in the presence of healthy plasma. AAA tissues and SMCs have a higher ability to promote fibrin formation, to activate prothrombin, and to mobilize the tissue factor (TF) pathway, whereas TAA tissues and derived SMCs express an anti-thrombotic phenotype. Activation of the TF pathway in AAA tissue and SMCs is provoked by oxidative stress, protease-activated receptor 2 (PAR-2) overexpression and nuclear factor-kappa B (NF-κB) mobilization which could be reproduced by SMC efferocytosis of senescent red blood cells. Moreover, the high coherence between what was observed ex vivo in tissue and in passaged SMCs in vitro, demonstrated a procogulant phenotype shift in AAA SMCs, potentially as an imprinting of environmental pro-oxidative conditions of AAA. Conclusion: Our data indicate that oxidative stress-induced activation of the PAR-2 - NF-κB axis and leads to an increase in TF activity and prothrombotic properties of SMCs from AAA. [ABSTRACT FROM AUTHOR]

Background and Objectives: Glycocalyx, a thin layer of carbohydrates covering endothelial cells, is important for interactions between blood components and the vascular wall. It is implicated in circulating cells adhesion, inflammation, and coagulation regulation and can be damaged in some diseases. The prevailing hypothesis is that hypertension is the primary factor involved in glycocalyx degradation. However, our preliminary data challenge this view and point to a more important role of inflammation. The objective of this study was to assess the respective roles of inflammation and hemodynamic on the endothelial glycocalyx degradation. Methods and Results: Plasma concentrations of syndecan-1, a glycocalyx degradation marker, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 were quantified by ELISA in 327 participants (62 ± 14 years). Subjects were categorized as atherosclerotic cardio-vascular diseases (ASCVD) patients or controls and performed all a blood pressure and pulse wave velocity assessment. Syndecan-1 was positively associated with circulating IL-6 (p < 0.001), IL-8 (p = 0.002), and IL-10 concentrations (p = 0.006) and with adhesion molecules ICAM-1 and VCAM-1 (p < 001). No relation was observed between syndecan-1 and hemodynamic parameters, thus confirming the major role of inflammatory status in the degradation of endothelial glycocalyx. Interestingly, subjects with higher plasma concentration of syndecan-1 (third tertile) displayed more clinical manifestation of atherosclerosis (65 vs 42%; p < 0.001) than those with lower concentration (first tertile). Conclusions: Endothelial glycocalyx degradation is rather associated with inflammatory status than hemodynamic parameters. Higher degradation of glycocalyx is associated with increased percentage of ASCVD suggesting a direct relation between glycocalyx degradation and increased risk of atherosclerotic diseases. [ABSTRACT FROM AUTHOR]

Background: Ctip2/Bcl11b is a transcription factor with dual action (repression/activation) that couples epigenetic regulation to gene transcription in a variety of physiological responses under healthy and pathological conditions of various tissues. Single nucleotide polymorphisms of Ctip2/Bcl11b gene are associated with a higher susceptibility for aortic stiffness (1). although Ctip2/Bcl11b has been proposed as a crucial regulator of aortic smooth muscle function (2), its mechanism of action in smooth muscle cells is still to be uncovered. Methods: Morphological, cellular and molecular analysis were carried out on the arteries of smooth muscle cell-specific Ctip2-knockout (KO) mice at 3, 7, 28 days after tamoxifen injections. Results: There is no difference between control and mutant mice at the macroscopic level 3 days after Ctip2 KO induction, however, 7 day after Bcl11b inactivation, 65% of the Ctip2-SMKO mice showed signs of hemorrhage in the distal part of the thoracic aorta near the abdominal aorta. The histological examination of thoracic aorta at 7 indicated the presence of "bumpy region" in the mutant aorta. These areas is covered by a thicker layer of extracellular matrix and the presence of IgG positive cells, indicating that cell death is occurring. However, the hemorrhages is contained over time, do not impact mice survival. qPCR analysis indicated the altered expression of circadian-related genes such as genes of Bmal and ciart. Conclusions: Our data indicate the primary effect of Bcl11b inactivation on cell death, probably by necroptosis. [ABSTRACT FROM AUTHOR]

Objective: Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the oxidation of primary amines into ammonia and reactive species (hydrogen peroxide, aldehydes). It is highly expressed in mammalian tissues, especially in vascular smooth muscle cells and adipocytes, where it plays a role in cell differentiation and glucose transport. The study aims at characterizing the expression and the activity of SSAO in rat and human articular cartilage of the knee, and to investigate its potential role in chondrocyte terminal differentiation.Design: SSAO expression was examined by immunohistochemistry and western blot. Enzyme activity was measured using radiolabeled benzylamine as a substrate. Primary cell cultures of rat chondrocytes were treated for 21 days by a specific SSAO inhibitor, LJP 1586. Terminal chondrocyte differentiation markers were quantified by RT-qPCR. The basal and IL1β-stimulated glucose transport was monitored by the entrance of (3)[H]2-deoxyglucose in chondrocytes.Results: SSAO was expressed in chondrocytes of rat and human articular cartilage. SSAO expression was significantly enhanced during the hypertrophic differentiation of chondrocytes characterized by an increase in MMP13 and in alkaline phosphatase (ALP) expressions. SSAO inhibition delayed the late stage of chondrocyte differentiation without cell survival alteration and diminished the basal and IL1β-stimulated glucose transport. Interestingly, SSAO activity was strongly increased in human osteoarthritic cartilage.Conclusions: SSAO was expressed as an active form in rat and human cartilage. The results suggest the involvement of SSAO in rat chondrocyte terminal differentiation via a modulation of the glucose transport. In man, the increased SSAO activity detected in osteoarthritic patients may trigger hypertrophy and cartilage degeneration. [ABSTRACT FROM AUTHOR]

The article discusses a study which assess the role of functional genetic variants for stiffness and plasma lipids of carotid artery. It states that an analysis for monomorphic variants of alleles was conducted for sample taken from study subjects. It reveals the involvement of gene CLEC16A for carotid vasodilatation modulation.

Arterial stiffening is a strong independent risk factor for cardiovascular disease. B-cell leukaemia 11b (BCL11B) is a transcription factor known as an essential regulator in T lymphocytes differentiation and neuronal development. Several genome-wide association studies showed that single nucleotide polymorphisms (SNPs) in the 3'gene desert of Bcl11b are associated with a higher susceptibility for aortic stiffness and blood pressure control. However, its role in smooth muscle cells and mechanism of action remains to be uncovered. Our aims are: (1) to analyse the role of Bcl11b in vascular system; (2) to characterize the signalling pathways related to Bcl11b in cell death. Morphological, cellular and molecular analysis were carried out on the arteries of smooth muscle cell-specific Bcl11b-knockout mice at 3, 7, 28 days after tamoxifen injections as well as on the smooth muscle cells isolated from the aorta of Bcl11b-floxed mice that were cultured and inactivated by Cre recombinase using adenoviral vectors. We analysed mice with Bcl11b deletion in vascular SMC (Bcl11b-SMKO). There is no difference between control and mutant mice at the macroscopic level 3 days after Bcl11b KO induction, however, 7 days after Bcl11b inactivation, 70% of the Bcl11b-SMKO mice showed signs of haemorrhage in the distal part of the thoracic aorta near the abdominal aorta. The histological examination of thoracic aorta at day 7 indicated the presence of "bumpy region" in the mutant aorta, these areas seem to be covered by a thicker layer of extracellular matrix and the presence of IgG positive cells, indicating that cell death via necroptosis is occurring in this tissue. Our preliminary results from smooth muscle cell culture indicate higher cell death rate in the mutant cells compared to control cells. Our data suggest a primary effect of Bcl11b inactivation on cell death, probably through necroptosis. The mechanisms linked to cell death induced by Bcl11b loss is under investigation. [ABSTRACT FROM AUTHOR]

Arterial stiffness is recognized as a risk factor for many cardiovascular diseases. Aldosterone via its binding to and activation of the mineralocorticoid receptors (MRs) is a main regulator of blood pressure by controlling renal sodium reabsorption. Although both clinical and experimental data indicate that MR activation by aldosterone is involved in arterial stiffening, the molecular mechanism is not known. In addition to the kidney, MR is expressed in both endothelial and vascular smooth muscle cells (VSMCs), but the specific contribution of the VSMC MR to aldosterone-induced vascular stiffness remains to be explored. To address this question, we generated a mouse model with conditional inactivation of the MR in VSMC (MR(SMKO)). MR(SMKO) mice show no alteration in renal sodium handling or vascular structure, but they have decreased blood pressure when compared with control littermate mice. In vivo at baseline, large vessels of mutant mice presented with normal elastic properties, whereas carotids displayed a smaller diameter when compared with those of the control group. As expected after aldosterone/salt challenge, the arterial stiffness increased in control mice; however, it remained unchanged in MR(SMKO) mice, without significant modification in vascular collagen/elastin ratio. Instead, we found that the fibronectin/α5-subunit integrin ratio is profoundly altered in MR(SMKO) mice because the induction of α5 expression by aldosterone/salt challenge is prevented in mice lacking VSMC MR. Altogether, our data reveal in the aldosterone/salt hypertension model that MR activation specifically in VSMC leads to the arterial stiffening by modulation of cell-matrix attachment proteins independent of major vascular structural changes. [ABSTRACT FROM AUTHOR]

Although hypertension contributes significantly to worsen cardiovascular risk, blood pressure increment in subjects with heart failure is paradoxically associated with lower risk. The objective was to determine whether pulse pressure and pulse wave velocity (PWV) remain prognostic markers, independent of treatment in heart failure with reduced left ventricular function. The investigation involved 6632 patients of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study. All subjects had acute myocardial infarction with left ventricular ejection fraction <40% and signs/symptoms of heart failure. Carotid-femoral PWV was measured in a subpopulation of 306 subjects. In the overall population, baseline mean arterial pressure <90 mm Hg was associated with higher all-cause death (hazard ratio, 1.14 [95% confidence interval, 1.00-1.30]; P<0.05), whereas higher left ventricular ejection fraction or pulse pressure was associated with lower rates of all-cause death, cardiovascular death/hospitalization, and cardiovascular death. In the subpopulation, increased baseline PWV was associated with worse outcomes (all-cause death: 1.16 [1.03-1.30]; P<0.05 and cardiovascular deaths: 1.16 [1.03-1.31]; P<0.05), independent of age and left ventricular ejection fraction. Using multiple regression analysis, systolic blood pressure and age were the main independent factors positively associated with pulse pressure or PWV, both in the entire population or in the PWV substudy. In heart failure and low ejection fraction, our results suggest that pulse pressure, being negatively associated with outcome, is more dependent on left ventricular function and thereby no longer a marker of aortic elasticity. In contrast, increased aortic stiffness, assessed by PWV, contributes significantly to cardiovascular death. [ABSTRACT FROM AUTHOR]

Although hypertension contributes significantly to worsen cardiovascular risk, blood pressure increment in subjects with heart failure is paradoxically associated with lower risk. The objective was to determine whether pulse pressure and pulse wave velocity (PWV) remain prognostic markers, independent of treatment in heart failure with reduced left ventricular function. The investigation involved 6632 patients of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study. Al1 subjects had acute myocardial infarction with left ventricular ejection fraction <40% and signs/symptoms of heart failure. Carotid-femoral PWV was measured in a subpopulation of 306 subjects. In the overall population, baseline mean arterial pressure <90 mmHg was associated with higher all-cause death (hazard ratio, 1.14 [95% confidence interval, 1.00-1.30]; P<0.05), whereas higher left ventricular ejection fraction or pulse pressure was associated with 1ower rates of all-cause death, cardiovascular death/hospitalization, and cardiovascular death. In the subpopulation, increased baseline PWV was associated with worse outcomes (all-cause death: 1.16 [1.03-1.30]; P<0.05 and cardiovascular deaths: 1.16 [1.03-1.31]; P<0.05), independent of age and left ventricular ejection fraction. Using multiple regression analysis, systolic blood pressure and age were the main independent factors positively associated with pulse pressure or PWV, both in the entire population or in the PWV substudy. In heart failure and low ejection fraction, our results suggest that pulse pressure, being negatively associated with outcome, is more dependent on left ventricular function and thereby no longer a marker of aortic elasticity. In contrast, increased aortic stiffness, assessed by PWV, contributes significantly to cardiovascular death. [ABSTRACT FROM AUTHOR]

Hypertension is a cardiovascular disorder that appears in more than half of the patients with Williams--Beuren syndrome, hemizygous for the elastin gene among 26 to 28 other genes. It was shown that the antihypertensive drug minoxidil, an ATP-dependent potassium channel opener, enhances elastic fiber formation; however, no wide clinical application was developed because of its adverse side effects. The Brown Norway rat was used here as an arterial elastin--deficient model. We tested 3 different potassium channel openers, minoxidil, diazoxide, and pinacidil, and 1 potassium channel blocker, glibenclamide, on cultured smooth muscle cells from Brown Norway rat aorta. All tested potassium channel openers increased mRNAs encoding proteins and enzymes involved in elastic fiber formation, whereas glibenclamide had the opposite effect. The higher steady-state level of tropoelastin mRNA in minoxidil-treated cells was attributable to an increase in both transcription and mRNA stability. Treatment of Brown Norway rats for 10 weeks with minoxidil or diazoxide increased elastic fiber content and decreased cell number in the aortic media, without changing collagen content. The minoxidil-induced cardiac hypertrophy was reduced when animals simultaneously received irbesartan, an angiotensin II--receptor antagonist. This side effect of minoxidil was not observed in diazoxide-treated animals. In conclusion, diazoxide, causing less undesirable side effects than minoxidil, or coadministration of minoxidil and irbesartan, increases elastic fiber content, decreases cell number in the aorta and, thus, could be suitable for treating vascular pathologies characterized by diminished arterial elastin content and simultaneous hypertension. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study that examines the association of the absence of cardiotrophin 1 (CT-1), an interleukin 6 family, with arterial fibrosis and stiffness, senescence and life span. Chronic CT-1 stimulation upregulated apoptotic and senescence markers and downregulated telomere-linked proteins in vascular smooth muscle cells. It concludes that CT-1 may be a major arterial stiffness regulator.

The article explores the role of cardiotrophin 1 (CT-1) in cardiac, vascular and renal fibrosis and dysfunction. In their study, the authors utilized M-mode echocardiography, Doppler and echo tracking device and ex vivo-acoustic microscopy method to analyze cardiac and vascular functions. They found that increased left ventricular volumes were seen after CT-1 treatment, which also caused increased vascular media thickness and fibronectin content.

The article reviews the relationship of sodium intake and vascular stiffness in hypertension. It discusses the influence of dietary sodium on vascular stiffness and its role in the modulation of stroke volume and systolic blood pressure through mechanisms affecting the venous circulation. It explains the adverse effect of sodium intake on arterial circulation and how it worsens hypertension and exacerbates cardiovascular risk. A summary of sodium and blood pressure interactions with the renin-angiotensin-aldosterone system is given.

Semicarbazide-sensitive amine oxidase (SSAO)-deficient mice present no alteration in elastin cross-linking processes and carotid mechanical properties. In contrast, previous studies have shown that SSAO inhibitors induced marked anomalies in arterial structure and function. The aim of the present study was to examine the effect of semicarbazide (SCZ), an efficient SSAO inhibitor, on the arterial phenotype of the carotid artery in relation to modulation of SSAO and lysyl oxidase activities in growing rats. We first show that after 6 weeks of SCZ treatment (100 mg/kg per day), SSAO activity was reduced by 90%, whereas lysyl oxidase activity was only partially inhibited (<60%) in carotid artery, compared with controls. There was significant growth inhibition and no difference in mean arterial pressure but an increase in pulse pressure with a smaller arterial diameter in SCZ-treated rats. SCZ decreased aortic insoluble elastin without a change in total collagen. In addition, extracellular proteins other than insoluble elastin and collagen were increased in SCZ-treated rats. All of the elastic lamellae presented globular masses along their periphery, and focal disorganization was observed in the ascending aorta. Carotid artery mechanical strength was lower in SCZ-treated rats, and the elastic modulus-wall stress curve was shifted leftward compared with controls, indicating increased stiffness. Thus, SCZ modifies arterial geometry and mechanical properties, alters elastic fiber structure, and reduces the content of cross-linked elastin. Because these abnormalities are essentially absent in SSAO-deficient mice, our results suggest that lysyl oxidase inhibition is responsible for the major part of the vascular phenotype of SCZ-treated rats. [ABSTRACT FROM AUTHOR]

Summary: Arterial stiffness has an independent predictive value for cardiovascular events. This review proposes an integrated view of the molecular determinants of arterial stiffness, based on a candidate gene approach, an analysis of the structure–function relationship in hypertension, and studies on gene expression profile in humans. In monogenic diseases of connective tissue (Marfan, Williams, and Ehlers–Danlos syndromes) and corresponding animal models, the precise characterization of arterial phenotype allows understanding the influence of abnormal, genetically determined, wall components on arterial stiffness. These studies underline the role of extra-cellular matrix signaling in the vascular wall and the fact that elastin and collagen have not only passive elastic or rigid properties, but also are implicated in the control of SMC function. In animal models of essential hypertension (SHR and SHR-SP), the structural modifications of the arterial wall include a higher number of elastin/SMC connections, and smaller fenestrations of the internal elastic lamina, which could redistribute the mechanical load towards elastic materials. Thus, the changes in arterial wall material which accompany wall hypertrophy in these animals are not associated with an increased stiffness. Taken together, these data afford strong arguments to consider that arterial stiffness is not only influenced by the amount and density of stiff wall material, but mainly by its spatial organization. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel diseases (IBD) have an increased risk of thrombosis, possibly due to changes in blood cells and molecules involved in hemostasis. They have increased platelet counts and reactivity as well as increased platelet-derived large extracellular vesicles. Coagulation is continuously activated in patients with IBD, based on measured markers of thrombin generation, and the anticoagulant functions of endothelial cells are damaged. Furthermore, fibrinogen is increased and fibrin clots are denser. However, pathogenesis of thrombosis in patients with IBD appears to differ from that of patients without IBD. Patients with IBD also take drugs that might contribute to risk of thrombosis, complicating the picture. We review the features of homeostasis that are altered in patients with IBD and possible mechanisms of this relationship. [ABSTRACT FROM AUTHOR]