scholarly journals Coronary Artery Spasm: The Interplay Between Endothelial Dysfunction and Vascular Smooth Muscle Cell Hyperreactivity

2020 ◽  
Vol 15 ◽  
Author(s):  
Astrid Hubert ◽  
Andreas Seitz ◽  
Valeria Martínez Pereyra ◽  
Raffi Bekeredjian ◽  
Udo Sechtem ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Chest Pain ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Coronary Artery Spasm ◽  
Cardinal Symptom

Patients with angina pectoris, the cardinal symptom of myocardial ischaemia, yet without significant flow-limiting epicardial artery stenosis represent a diagnostic and therapeutic challenge. Coronary artery spasm (CAS) is an established cause for anginal chest pain in patients with angiographically unobstructed coronary arteries. CAS may occur at the epicardial level and/or in the microvasculature. Although the underlying pathophysiological mechanisms of CAS are still largely unclear, endothelial dysfunction and vascular smooth muscle cell (VSMC) hyperreactivity seem to be involved as major players, although their contribution to induce CAS is still seen as controversial. This article will look at the role and possible mechanistic interplay between an impaired endothelial and VSMC function in the pathogenesis of CAS.

scholarly journals Associations between Vaspin Levels and Coronary Artery Disease

2020 ◽  
Vol 4 (3) ◽  
pp. 211-216
Author(s):  
Lutfu Askin ◽  
Okan Tanriverdi ◽  
Hakan Tibilli ◽  
Serdar Turkmen
Keyword(s):  
Coronary Artery Disease ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Foam Cell ◽  
Foam Cell Formation ◽  
Artery Disease

The relationship between serum vaspin levels and metabolic or coronary artery disease is currently of interest for researchers. Although adipokine concentrations have been shown to be increased significantly in atherosclerotic lesions, the role adipokines in the atherosclerotic process remains to be elucidated. Vaspin is a new biological marker associated with obesity and impaired insulin sensitivity. Plasma vaspin concentration has been shown to correlate with the severity of coronary artery disease. Vascular inflammation triggered by vaspin inhibits atherogenesis by suppressing macrophage foam cell formation and vascular smooth muscle cell migration and proliferation. Vaspin also contributes to plaque stabilization by increasing collagen content and reducing the intraplaque macrophage to vascular smooth muscle cell ratio. The therapeutic goal concerning vaspin is to fight atherosclerosis and related diseases, as well as to maintain vascular health.

scholarly journals Reduced Platelet miR-223 Induction in Kawasaki Disease Leads to Severe Coronary Artery Pathology Through a miR-223/PDGFRβ Vascular Smooth Muscle Cell Axis

2020 ◽  
Vol 127 (7) ◽  
pp. 855-873 ◽  
Author(s):  
Yuan Zhang ◽  
Yanfei Wang ◽  
Li Zhang ◽  
Luoxing Xia ◽  
Minhui Zheng ◽  
...  
Keyword(s):  
Cell Wall ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Lactobacillus Casei ◽  
Cell Wall Extract ◽  
Coronary Artery Pathology

Rationale: Kawasaki disease (KD) is an acute vasculitis of early childhood that can result in permanent coronary artery structural damage. The cause for this arterial vulnerability in up to 15% of patients with KD is unknown. Vascular smooth muscle cell dedifferentiation play a key role in the pathophysiology of medial damage and aneurysm formation, recognized arterial pathology in KD. Platelet hyperreactivity is also a hallmark of KD. We recently demonstrated that uptake of platelets and platelet-derived miRNAs influences vascular smooth muscle cell phenotype in vivo. Objective: We set out to explore whether platelet/vascular smooth muscle cell (VSMC) interactions contribute to coronary pathology in KD. Methods and Results: We prospectively recruited and studied 242 patients with KD, 75 of whom had documented coronary artery pathology. Genome-wide miRNA sequencing and droplet digital PCR demonstrated that patient with KD platelets have significant induction of miR-223 compared with healthy controls (HCs). Platelet-derived miR-223 has recently been shown to promote vascular smooth muscle quiescence and resolution of wound healing after vessel injury. Paradoxically, patients with KD with the most severe coronary pathology (giant coronary artery aneurysms) exhibited a lack of miR-223 induction. Hyperactive platelets isolated from patients with KD are readily taken up by VSMCs, delivering functional miR-223 into the VSMCs promoting VSMC differentiation via downregulation of PDGFRβ (platelet-derived growth factor receptor β). The lack of miR-223 induction in patients with severe coronary pathology leads to persistent VSMC dedifferentiation. In a mouse model of KD ( Lactobacillus casei cell wall extract injection), miR-223 knockout mice exhibited increased medial thickening, loss of contractile VSMCs in the media, and fragmentation of medial elastic fibers compared with WT mice, which demonstrated significant miR-223 induction upon Lactobacillus casei cell wall extract challenge. The excessive arterial damage in the miR-223 knockout could be rescued by adoptive transfer of platelet, administration of miR-223 mimics, or the PDGFRβ inhibitor imatinib mesylate. Interestingly, miR-223 levels progressively increase with age, with the lowest levels found in <5-year-old. This provides a basis for coronary pathology susceptibility in this very young cohort. Conclusions: Platelet-derived miR-223 (through PDGFRβ inhibition) promotes VSMC differentiation and resolution of KD induced vascular injury. Lack of miR-223 induction leads to severe coronary pathology characterized by VSMC dedifferentiation and medial damage. Detection of platelet-derived miR-223 in patients with KD (at the time of diagnosis) may identify patients at greatest risk of coronary artery pathology. Moreover, targeting platelet miR-223 or VSMC PDGFRβ represents potential therapeutic strategies to alleviate coronary pathology in KD. Graphic Abstract: A graphic abstract is available for this article.

scholarly journals TCF7L2 Regulation of GATA6-dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia

2018 ◽  
Author(s):  
Roshni Srivastava ◽  
Harshavardhan Rolyan ◽  
Yi Xie ◽  
Na Li ◽  
Neha Bhat ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Intimal Hyperplasia ◽  
Adult Stem Cells ◽  
Artery Disease

AbstractGenetic variations in Wnt-coreceptor LRP6 and Wnt-regulated transcription factor TCF7L2 have been among the strongest genetic signals for type2 diabetes (T2DM) and coronary artery disease (CAD). Mice with a CAD-linked LRP6 mutation exhibit obstructive coronary artery disease characterized by reduced TCF7L2 expression and dedifferentiation of vascular smooth muscle cell (VSMC). While TCF7L2 maintains stemness and promotes proliferation in embryonic tissues and adult stem cells, its role and mechanisms of action in VSMC differentiation is not understood. Using multiple mouse models, we demonstrate here that TCF7L2 promotes differentiation and inhibits proliferation of VSMCs. TCF7L2 accomplishes these effects by stabilization of GATA6 and upregulation of SM-MHC and cell cycle inhibitors. Accordingly, TCF7L2 haploinsufficient mice exhibited increased susceptibility to, while mice overexpressing TCF7L2 were protected against injury-induced intimal hyperplasia compared to wildtype littermates. Consequently, the overexpression of TCF7L2 in LRP6 mutant mice rescued the injury induced intimal hyperplasia. These novel findings imply cell type-specific functional role of TCF7L2 and provide critical insight into poorly understood mechanisms underlying pathogenesis of intimal hyperplasia.

scholarly journals Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Ting-Yan Yu ◽  
Xin-Xin Chen ◽  
Qing-Wen Liu ◽  
Fang-Fang Ma ◽  
Hong-Lang Huang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Cell Phenotype ◽  
Phenotypic Modulation ◽  
C Terminus ◽  
And Migration

Coronary artery disease (CAD) has been the leading cause of morbidity and mortality worldwide, and its pathogenesis is closely related with the proliferation and migration of vascular smooth muscle cell (VSMC). We previously reported a truncated GATA4 protein lacking C-terminus induced by p.S335X mutation in cardiomyocyte from ventricular septal defect (VSD) patients. However, it is still unclear whether GATA4 p.S335X mutation could influence the development of CAD. GATA4 wild-type (WT) and p.S335X mutant (MU) overexpression plasmids were constructed and transfected transiently into rat coronary artery smooth muscle cell (RCSMC) to observe the proliferative and migratory abilities by MTS and wound healing assay, respectively. PCR array was used to preliminarily detect the expression of phenotypic modulation-related genes, and QRT-PCR was then carried out to verify the screened differentially expressed genes (DEGs). The results showed that, when stimulated by fetal bovine serum (10%) for 24 h or tumor necrosis factor-α (10 or 30 ng/ml) for 10 or 24 h, deletion of GATA4 C-terminus by p.S335X mutation in GATA4 enhanced the proliferation of RCSMC, without alteration of the migration capability. Twelve DEGs, including Fas, Hbegf, Itga5, Aimp1, Cxcl1, Il15, Il2rg, Il7, Tnfsf10, Il1r1, Irak1, and Tlr3, were screened and identified as phenotypic modulation-related genes. Our data might be beneficial for further exploration regarding the mechanisms of GATA4 p.S335X mutation on the phenotypic modulation of coronary VSMC.

Abstract 15505: Aortic Stiffening in L-NAME Treated C57bl6 Mice Precedes Peripheral Hypertension and Cardiac Hypertrophy: Early Endothelial Dysfunction Shifts to Late-term Vascular Smooth Muscle Cell Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sofie De Moudt ◽  
Jhana O Hendrickx ◽  
Dorien G De Munck ◽  
Arthur Leloup ◽  
Wim Martinet ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Endothelial Dysfunction ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Cardiac Disease ◽  
Ex Vivo ◽  
Fast Onset ◽  
Aortic Stiffening

Introduction: Endothelial dysfunction (ED) acts as a common player in most cardiovascular (CV) risk factors (e.g. hypertension, smoking) underlining its importance in CV ageing. Therefore, this study aims to characterize ex vivo aortic function changes in Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) treated mice. Methods: C57Bl6 mice (male, n=10) received 0.5 mg/mL L-NAME through the drinking water for 1, 2, 4, 8, and 16 weeks, followed by in-depth ex vivo thoracic aorta isometric reactivity studies and arterial stiffness (Peterson modulus, Ep) measurements in the Rodent Oscillatory Tension set-up for Arterial Compliance (ROTSAC). In addition, peripheral blood pressure (BP, Coda), aortic pulse wave velocity (aPWV, Vevo2100), and echocardiography (Vevo2100) were measured in vivo . (Data are represented as mean±SEM) Results: L-NAME treated mice display fast-onset aortic stiffening after 1-week L-NAME (Fig. A, B), followed by the development of peripheral hypertension (Fig. C) and cardiac disease (Fig. D-F) after 4-weeks L-NAME. Ex vivo aorta studies reveal different stages of disease. Early on (1-4 weeks), mice show elevated phenylephrine (PE) contractions (Fig. G) and impaired acetylcholine (ACh) relaxations (Fig. H), consistent with L-NAME related ED. After 8 weeks, endothelial function and PE contractions normalize. Relaxations to exogenous NO remain unaltered (Fig. I). In contrast to the recovery of ACh relaxations, stiffness analysis in the ROTSAC reveals constantly reduced basal NO levels (Fig. J), and a late-term shift (16 weeks) towards vascular smooth muscle cell (VSMC) disease. This involves basal cytoplasmic calcium loading (Fig. K) and a sharply increasing contribution of voltage-gated calcium channels (Fig. L). Conclusions: NOS inhibition by L-NAME treatment causes a distinct time-dependent aortic disease phenotype, underlying fast-onset arterial stiffening which precedes peripheral hypertension and cardiac disease.

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