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Abstract Background Negative coronary artery remodeling is frequent in patients with diabetes, but its mechanism remains unclear. We here evaluated the association of serum levels of glycated albumin (GA) and endogenous secretory receptor for advanced glycation end products (esRAGE) with coronary artery remodeling in type 2 diabetic patients. Methods Serum levels of GA and esRAGE were measured and intravascular ultrasound was performed in 136 consecutive diabetic patients with 143 coronary intermediate lesions. The remodeling index (RI) was calculated as the ratio between external elastic membrane (EEM) area at the lesion site and EEM area at the reference segment. Negative remodeling (NR) was defined as an RI

Fractional flow reserve (FFR) may not be immune from hemodynamic perturbations caused by both vessel and lesion related factors. The aim of this study was to investigate the impact of plaque- and vessel wall-related features of vulnerability on the hemodynamic effect of intermediate coronary stenoses. Methods and Results: In this cross-sectional study, patients referred to catheterization laboratory for clinically indicated coronary angiography were prospectively screened for angiographically intermediate stenosis (50–80%). Seventy lesions from 60 patients were evaluated. Mean angiographic stenosis was 62.1 ± 16.3%. After having performed FFR assessment, intravascular ultrasound (IVUS) was performed over the FFR wire. Virtual histology IVUS was used to identify the plaque components and thin cap fibroatheroma (TCFA). TCFA was significantly more frequent (65 vs. 38%, p = 0.026), and necrotic core volume (26.15 ± 14.22 vs. 16.21 ± 8.93 mm3, p = 0.04) was significantly larger in the positively remodeled than non-remodeled vessels. Remodeling index correlated with necrotic core volume (r = 0.396, p = 0.001) and with FFR (r = –0. 419, p = 0.001). With respect to plaque components, only necrotic core area (r = –0.262, p = 0.038) and necrotic core volume (r = –0.272, p = 0.024) were independently associated with FFR. In the multivariable model, presence of TCFA was independently associated with significantly lower mean FFR value as compared to absence of TCFA (adjusted, 0.71 vs. 0.78, p = 0.034). Conclusion: The current study demonstrated that for a given stenosis geometry, features of plaque vulnerability such as necrotic core volume, TCFA, and positive remodeling may influence the hemodynamic relevance of intermediate coronary stenoses. [ABSTRACT FROM AUTHOR]

Objective: The histological characteristics of plaque may affect the hemodynamic outcome of a given coronary stenosis. In particular, the potential effect of volumetric calcium content and the topographical distribution in the lesion segment on physiological outcome has not yet been investigated. The aim of this study was to identify any potential correlation between patterns of calcification and the fractional flow reserve (FFR) and the coronary remodeling index (RMI). Methods: A total of 26 stable angina pectoris and 34 acute coronary syndrome patients without persistent ST-segment elevation constituted the study population. FFR was used to assess 70 intermediate coronary stenosis lesions. After obtaining hemodynamic measurements, quantitative grayscale and virtual histology-intravascular ultrasound analyses were performed. The depth, length, and circumferential distribution of calcification of the lesions were also recorded. Results: Within the analyzed segment (area of interest, lesion segment), FFR was correlated with maximal thickness of deep calcification (r=-0.285; p=0.021) and calcification angle (r=-0.396; p=0.001). In lesions with a calcification angle >180°, the mean FFR value was significantly lower compared with those

Objectives: Coronary onlay grafting, with or without endarterectomy, has been widely used for the treatment of diffuse lesions. Recent studies have demonstrated excellent long-term patency and favorable remodeling of onlay anastomosis; however, the underlying mechanisms remain unknown. Here, we describe the mechanism of intimal regeneration based on postmortem pathological evaluation of a patient who had undergone onlay grafting with coronary endarterectomy. Methods: The onlay anastomosis was analyzed using a combination of immunohistological stainings, namely, H&E, vimentin, α-SMA, factor VIII, and Ki-67, to identify the source and mechanism of intimal regeneration after onlay grafting with endarterectomy. Results: Our results suggest that the regenerated endothelium derives from the smooth muscle cells of the endarterectomized media of the coronary artery and that it circumferentially covers the internal lumen of the arterial graft. Conclusions: Intimal regeneration, derived from the smooth muscle cells of the endarterectomized coronary artery that proliferate toward the graft lumen, may be a key mechanism that underlies the observed favorable remodeling after onlay grafting during coronary endarterectomy. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is suggested to cause an “early vascular aging” phenomenon that is associated with vascular dysfunction, remodeling, and adverse alterations in vascular stiffness. Given that both T2DM and aging are prominent risk factors for cardiovascular disease, the aim of this study was to test the hypothesis that coronary resistance microvessel (CRM) remodeling and impairments in flow occur in the compound setting of T2DM and aging. Normal heterozygous Db/db controls and homozygous db/db mice were aged to 16 (young) or 36 (aged) weeks for all experiments and passive pressure myography and echocardiography were used to assess vascular mechanics, and structure. CRM wall thickness was significantly increased at each pressure in aged control mice compared to young control mice (9.4 ± 0.6 vs. 6.8 ± 0.2 μm, respectively, p < 0.001); however, there were no significant differences in CRM wall thickness of aged db/db mice vs. young db/db mice. Aged control mice had a higher medial CSA compared to young control mice (3847 ± 303 vs. 2715 ± 170 μm2, p < 0.01); however, there were no significant differences in medial CSA of aged db/db mice vs. young db/db mice. Elastic modulus was lower in aged control CRMs vs. young control CRMs (3.5x106± 0.7 × 106 vs. 8.7 × 106± 0.6 × 106, p < 0.0001). Elastic modulus remained the same in young db/db mice vs. aged db/db mice. These data show that the diabetic CRMs undergo adverse remodeling at an early age, similar to normal aged CRMs, that persists toward senescence, and it further suggests that diabetic CRMs are subject to an early aging phenomenon.

Type 2 diabetes mellitus (T2DM) is suggested to cause an "early vascular aging" phenomenon that is associated with vascular dysfunction, remodeling, and adverse alterations in vascular stiffness. Given that both T2DM and aging are prominent risk factors for cardiovascular disease, the aim of this study was to test the hypothesis that coronary resistance microvessel (CRM) remodeling and impairments in flow occur in the compound setting of T2DM and aging. Normal heterozygous Db/db controls and homozygous db/db mice were aged to 16 (young) or 36 (aged) weeks for all experiments and passive pressure myography and echocardiography were used to assess vascular mechanics, and structure. CRM wall thickness was significantly increased at each pressure in aged control mice compared to young control mice (9.4 ± 0.6 vs. 6.8 ± 0.2 μm, respectively, p < 0.001); however, there were no significant differences in CRM wall thickness of aged db/db mice vs. young db/db mice. Aged control mice had a higher medial CSA compared to young control mice (3847 ± 303 vs. 2715 ± 170 μm2, p < 0.01); however, there were no significant differences in medial CSA of aged db/db mice vs. young db/db mice. Elastic modulus was lower in aged control CRMs vs. young control CRMs (3.5x106± 0.7 × 106 vs. 8.7 × 106± 0.6 × 106, p < 0.0001). Elastic modulus remained the same in young db/db mice vs. aged db/db mice. These data show that the diabetic CRMs undergo adverse remodeling at an early age, similar to normal aged CRMs, that persists toward senescence, and it further suggests that diabetic CRMs are subject to an early aging phenomenon. [ABSTRACT FROM AUTHOR]

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The aim of the present study was to evaluate the role of magnetic resonance imaging (MRI) for the non-invasive detection of coronary abnormalities and specifically the remodeling process in patients with coronary artery disease (CAD). MRI was performed in 10 control healthy subjects and 26 patients with angiographically proven CAD of the right coronary (RCA) or left anterior descending (LAD) artery; 23 patients were within two months of acute coronary syndromes, and 3 had stable angina with a positive test for ischemia. Wall thickness (WT), vessel wall area (VWA), total vessel area (TVA), and luminal area (LA) were measured. There were significant increases in WT (mean ± SEM, RCA: 2.62 ± 0.75 vs 0.53 ± 0.15 mm; LAD: 2.21 ± 0.69 vs 0.62 ± 0.24 mm) and in VWA (RCA: 30.96 ± 17.57 vs 2.1 ± 1.2 mm²; LAD: 19.53 ± 7.25 vs 3.6 ± 2.0 mm²) patients compared to controls (P < 0.001 for each variable). TVA values were also greater in patients compared to controls (RCA: 44.56 ± 21.87 vs 12.3 ± 4.2 mm²; LAD: 31.89 ± 11.31 vs 17.0 ± 6.2 mm²; P < 0.001). In contrast, the LA did not differ between patients and controls for RCA or LAD. When the LA was adjusted for vessel size using the LA/TVA ratio, a significant difference was found: 0.33 ± 0.16 in patients vs 0.82 ± 0.09 in controls (RCA) and 0.38 ± 0.13 vs 0.78 ± 0.06 (LAD) (P < 0.001). As opposed to normal controls, positive remodeling was present in all patients with CAD, as indicated by larger VWA. We conclude that MRI detected vessel wall abnormalities and was an effective tool for the noninvasive evaluation of the atherosclerotic process and coronary vessel wall modifications, including positive remodeling that frequently occurs in patients with acute coronary syndromes.

Abstract: The goals of the present study were to compare coronary resistance microvessel (CRM) remodeling between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) mice, and to determine the impact of aerobic exercise training on CRM remodeling in diabetes. Eight week old male mice were divided into T1DM: control sedentary (Control-SD), T1DM sedentary (T1DM-SD) induced by streptozotocin, and T1DM exercise trained (T1DM-TR); T2DM: control sedentary (Db/db-SD), T2DM sedentary (db/db-SD), and T2DM trained (db/db-TR). Aerobic exercise training (TR) was performed on a mouse treadmill for 8weeks. CRMs were isolated and mounted on a pressure myograph to measure and record vascular remodeling and mechanics. CRM diameters, wall thickness, stress–strain, incremental modulus remained unchanged in T1DM-SD mice compared to control, and exercise training showed no effect. In contrast, CRMs isolated from db/db-SD mice exhibited decreased luminal diameter with thicker microvascular walls, which significantly increased the wall:lumen ratio (Db/db-SD: 5.8±0.3 vs. db/db-SD: 8.9±0.7, p <0.001). Compared to db/db-SD mice, coronary arterioles isolated from db/db-TR mice had similar internal diameter and wall thickness, while wall:lumen ratio (6.8±0.2, p <0.05) and growth index (db/db-SD: 16.2 vs. db/db-TR: 4.3, % over Db/db) were reduced. These data show that CRMs undergo adverse inward hypertrophic remodeling only in T2DM, but not T1DM, and that aerobic exercise training can partially mitigate this process. [Copyright &y& Elsevier]

Background: Negative coronary artery remodeling is frequent in patients with diabetes, but its mechanism remains unclear. We here evaluated the association of serum levels of glycated albumin (GA) and endogenous secretory receptor for advanced glycation end products (esRAGE) with coronary artery remodeling in type 2 diabetic patients. Methods: Serum levels of GA and esRAGE were measured and intravascular ultrasound was performed in 136 consecutive diabetic patients with 143 coronary intermediate lesions. The remodeling index (RI) was calculated as the ratio between external elastic membrane (EEM) area at the lesion site and EEM area at the reference segment. Negative remodeling (NR) was defined as an RI < 0.95 and intermediate or positive remodeling as an RI ≥ 0.95. Results: Mean plaque burden at the lesion site was 70.96 ± 9.98%, and RI was 0.96 ± 0.18. Negative coronary arterial remodeling existed in 81 (56.6%) lesions. RI correlated closely with serum esRAGE level (r = 0.236, P = 0.005) and was inversely related to serum GA level (r = − 0.240, P = 0.004) and plasma low-density lipoprotein cholesterol (LDL-C) (r = − 0.206, P = 0.014) and total cholesterol levels (r = − 0.183, P = 0.028). Generalized estimating equations logistic regression analysis identified esRAGE (OR 0.037; 95% CI 0.012–0.564, P = 0.021), GA (OR 1.093; 95% CI 1.013–1.179, P = 0.018) and LDL-C (OR 1.479; 95% CI 1.072–2.835, P = 0.023) as independent predictors for negative remodeling. Conclusions: In diabetic patients, negative coronary artery remodeling is associated with increased GA and decreased esRAGE levels in serum. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary arterial hypertension (PAH) is a vascular disease not restricted to the lungs. Many signaling pathways described in PAH are also of importance in other vascular remodeling diseases, such as coronary artery disease (CAD). Intriguingly, CAD is 4× more prevalent in PAH compared with the global population, suggesting a link between these 2 diseases. Both PAH and CAD are associated with sustained inflammation and smooth muscle cell proliferation/apoptosis imbalance and we demonstrated in PAH that this phenotype is, in part, because of the miR-223/DNA damage/Poly[ADP-ribose] polymerase 1/miR-204 axis activation and subsequent bromodomain protein 4 (BRD4) overexpression. Interestingly, BRD4 is also a trigger for calcification and remodeling processes, both of which are important in CAD. Thus, we hypothesize that BRD4 activation in PAH influences the development of CAD., Approach and Results: PAH was associated with significant remodeling of the coronary arteries in both human and experimental models of the disease. As observed in PAH distal pulmonary arteries, coronary arteries of patients with PAH also exhibited increased DNA damage, inflammation, and BRD4 overexpression. In vitro, using human coronary artery smooth muscle cells from PAH, CAD and non-PAH-non-CAD patients, we showed that both PAH and CAD smooth muscle cells exhibited increased proliferation and suppressed apoptosis in a BRD4-dependent manner. In vivo, improvement of PAH by BRD4 inhibitor was associated with a reduction in coronary remodeling and interleukin-6 expression., Conclusions: Overall, this study demonstrates that increased BRD4 expression in coronary arteries of patient with PAH contributes to vascular remodeling and comorbidity development., (© 2017 American Heart Association, Inc.)