scholarly journals Effects of GLP‐1 receptor agonist on Ca2+ handling in coronary smooth muscle cells from metabolic syndrome Ossabaw swine with coronary artery disease

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Mikaela Lee McKenney ◽  
Daniel Suh ◽  
John Martin ◽  
Mouhamad Alloosh ◽  
Kyle Schultz ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Metabolic Syndrome ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Receptor Agonist ◽  
Muscle Cells ◽  
Coronary Smooth Muscle ◽  
Artery Disease

scholarly journals Metabolic Syndrome and SIRT1 Mutation Impair Ca2+ Channels in Coronary Smooth Muscle Cells of Ossabaw Miniature Swine

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Aish Thamba ◽  
John Reed ◽  
John S. Strobel ◽  
James Byrd ◽  
Mouhamad Alloosh ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Metabolic Syndrome ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Single Cells ◽  
Muscle Cells ◽  
Miniature Swine ◽  
Coronary Smooth Muscle ◽  
Artery Disease

Background: Changes in Ca2+ regulation have been implicated in various pathologies such as coronary artery disease and metabolic syndrome (MetS), thereby potentiating these diseases. Our lab has shown that MetS decreases voltage-gated Ca2+ channel (VGCC) activity and sarcoplasmic reticulum (SR) Ca2+ release in coronary smooth muscle cells and increases coronary artery disease in Ossabaw miniature swine. Furthermore, decreased SIRT1 enzyme function can impair Ca2+ signaling and increase coronary disease and MetS. We hypothesized that impaired SIRT1 and MetS would decrease VGCC function and SR calcium store. Methods: CRISPR/Cas9 methods delivered a leucine to proline point mutation in SIRT1 (SIRT1L100P) into the Ossabaw swine genome to compare to wild type (WT), mimicking the naturally occurring mutation in humans which decreases SIRT1 activity. Four treatment groups of juvenile swine were based on genotype and diet: WT Lean, SIRT1 Lean, WT MetS, and SIRT1 MetS. Lean swine were fed normal chow and MetS were fed a hypercaloric, atherogenic diet for 7 months. The left anterior descending coronary artery was harvested and enzymatically digested to obtain cells. Fluorescence microscopy measured the Ca2+ indicator fura-2 in single cells. Depolarization of cells with perfusion of 80 mM K+ was used to elicit Ca2+ influx through VGCC.  Caffeine (5 mM) exposure activated the Ca2+ release channel (ryanodine receptor) on the SR. Results: MetS was confirmed by increased body weight, impaired glucose tolerance, hyperinsulinemia, and hypercholesterolemia. Coronary atherosclerosis was shown by angiography, intravascular ultrasound, and gross imaging. A two-way analysis of variance revealed statistically significant overall effects of genotype (p=0.02), diet (p<0.0001), and an interaction (p<0.0001) between these variables to decrease VGCC function. In contrast, no effect was observed on SR Ca2+ release. Conclusion and Potential Impact: SIRT1 inhibition and MetS decreased VGCC function independently, but not additively or synergistically. (Support: NIH T35HL110854, DK120240, DK09751.)

scholarly journals TGFβ, smooth muscle cells and coronary artery disease: a review

2019 ◽  
Vol 53 ◽  
pp. 90-101 ◽  
Author(s):  
Emma L. Low ◽  
Andrew H. Baker ◽  
Angela C. Bradshaw
Keyword(s):  
Coronary Artery Disease ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Artery Disease

scholarly journals The Emerging Role of Long Non-coding RNAs and Circular RNAs in Coronary Artery Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Soudeh Ghafouri-Fard ◽  
Mahdi Gholipour ◽  
Mohammad Taheri
Keyword(s):  
Coronary Artery Disease ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Circular Rnas ◽  
Numerous Cell ◽  
Non Coding Rnas ◽  
Artery Disease

Coronary artery disease (CAD) is a common disorder caused by atherosclerotic processes in the coronary arteries. This condition results from abnormal interactions between numerous cell types in the artery walls. The main participating factors in this process are accumulation of lipid deposits, endothelial cell dysfunction, macrophage induction, and changes in smooth muscle cells. Several lines of evidence underscore participation of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in the pathogenesis of CAD. Several lncRNAs such as H19, ANRIL, MIAT, lnc-DC, IFNG-AS1, and LEF1-AS1 have been shown to be up-regulated in the biological materials obtained from CAD patients. On the other hand, Gas5, Chast, HULC, DICER1-AS1, and MEG3 have been down-regulated in CAD patients. Meanwhile, a number of circRNAs have been demonstrated to influence function of endothelial cells or vascular smooth muscle cells, thus contributing to the pathogenesis of CAD. In the current review, we summarize the function of lncRNAs and circRNAs in the development and progression of CAD.

scholarly journals Genetic Regulatory Mechanisms of Smooth Muscle Cells Map to Coronary Artery Disease Risk Loci

2018 ◽  
Vol 103 (3) ◽  
pp. 377-388 ◽  
Author(s):  
Boxiang Liu ◽  
Milos Pjanic ◽  
Ting Wang ◽  
Trieu Nguyen ◽  
Michael Gloudemans ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Disease Risk ◽  
Muscle Cells ◽  
Regulatory Mechanisms ◽  
Coronary Artery Disease Risk ◽  
Artery Disease

Abstract 465: Deciphering the Genetic Regulation of ADAMTS7 , a Novel Locus for Coronary Artery Disease

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Kristy Ou ◽  
Robert C Bauer ◽  
Xuan Zhang ◽  
Jian Cui ◽  
Daniel J Rader ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Cell Lines ◽  
Genetic Regulation ◽  
Muscle Cells ◽  
Cell Types ◽  
Artery Disease ◽  
Genomic Regions

Recent genome-wide association studies (GWAS) have identified an association between the ADAMTS7 locus and coronary artery disease (CAD) in humans. While ADAMTS7 is proposed to play a role in vascular smooth muscle cell (VSMC) migration and neointimal formation, the molecular regulation of human ADAMTS7 gene expression has not yet been explored. We assessed ADAMTS7 expression levels in primary mouse aortic smooth muscle cells (mAoSMC) as well as primary human coronary and human pulmonary artery smooth muscle cells (hCASMC, hPASMC) in response to treatment with various stimulatory agents. No differences in ADAMTS7 expression were observed upon treatment with PDGF, angiotensin II, and nicotine in any of the cell lines tested. However, TNFα upregulated ADAMTS7 by 4-fold in mAoSMC but not in human VSMCs while H 2 O 2 upregulated ADAMTS7 by 4-fold in hCASMC but not mAoSMCs. No agents modulated expression in hPASMC. Basal levels of ADAMTS7 varied among different VSMC lines; hCASMC had 2-fold greater levels of ADAMTS7 when compared to hPASMC and hAoSMC. These data demonstrate that ADAMTS7 is differentially regulated not only across different species, but also among different VSMC types, underscoring the complex genetic regulation of ADAMTS7 . In an attempt to elucidate important regulatory genomic regions controlling ADAMTS7 expression, we utilized data from the ENCODE project to identify regions surrounding ADAMTS7 that are enriched for regulatory domains, e.g. DNase hypsersensitivity (DHS) and H3K27 acetylation, in relevant cell types. We then overlayed data from CARDIoGRAM and C4D CAD GWAS to look for CAD-associated SNPs in these potential enhancers. Ultimately we selected 5 regions of interest (e.g., rs5029904 lies in region with increased H3K27 acetylation in ENCODE layered 7 cell lines, DHS peaks in serum fed and starved hAoSMCs, binding peaks for transcription factors via ENCODE ChIP-Seq experiments) for further studies in luciferase reporter assays multiple cell types to look for tissue specific expression mediated by these genomic regions. GWAS variants in these domains may affect the transcriptional regulation of ADAMTS7 , thus providing insight into the role for ADAMTS7 in human atherosclerosis.

Pathology of stable coronary artery disease

ESC CardioMed ◽  
2018 ◽  
pp. 1315-1320
Author(s):  
Michael Joner ◽  
Maria Isabel Castellanos ◽  
Anna Bulin ◽  
Kristin Steigerwald
Keyword(s):  
Coronary Artery Disease ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Necrotic Core ◽  
Intimal Thickening ◽  
Intraplaque Haemorrhage ◽  
Artery Disease ◽  
Plaque Destabilization

Coronary artery disease remains the major cause of morbidity and mortality on a global scale. Intimal thickening and fatty streaks represent early adaptive vascular changes, which are often regressive. Pathological intimal thickening represents the earliest progressive atherosclerotic lesion characterized by a focal accumulation of smooth muscle cells and acellular areas, often associated with lipid pools. Fibroatheroma is characterized by a necrotic core and can be split into early and late fibroatheroma, where macrophage apoptosis and defective efferocytosis play important roles in lesion progression. Intraplaque hypoxia is believed to result in neovascularization with subsequent intraplaque haemorrhage because of immature and leaky microvessels. Due to excessive cholesterol in remnants of erythrocyte membranes, intraplaque haemorrhage may result in rapid progression of necrotic core and plaque destabilization. Healed plaque rupture has been well delineated as an important mechanism of gradual luminal narrowing, where changes in collagen deposition allow recognition of rupture and healing sites. Calcification results from apoptosis of smooth muscle cells and macrophages or may also be caused by active release of cellular vesicles involved in calcium haemostasis. Extracellular matrix changes are associated with progression of atherosclerosis, while integrin signalling has been recognized as an important outside-in transcellular target of the inflammatory response.

scholarly journals Genetic regulatory mechanisms of smooth muscle cells map to coronary artery disease risk loci

2018 ◽  
Author(s):  
Boxiang Liu ◽  
Milos Pjanic ◽  
Ting Wang ◽  
Trieu Nguyen ◽  
Michael Gloudemans ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Regulatory Mechanisms ◽  
Human Populations ◽  
Genome Wide Association Studies ◽  
Artery Disease ◽  
Cad Risk

AbstractCoronary artery disease (CAD) is the leading cause of death globally. Genome-wide association studies (GWAS) have identified more than 95 independent loci that influence CAD risk, most of which reside in non-coding regions of the genome. To interpret these loci, we generated transcriptome and whole-genome datasets using human coronary artery smooth muscle cells (HCASMC) from 52 unrelated donors, as well as epigenomic datasets using ATAC-seq on a subset of 8 donors. Through systematic comparison with publicly available datasets from GTEx and ENCODE projects, we identified transcriptomic, epigenetic, and genetic regulatory mechanisms specific to HCASMC. We assessed the relevance of HCASMC to CAD risk using transcriptomic and epigenomic level analyses. By jointly modeling eQTL and GWAS datasets, we identified five genes (SIPA1, TCF21, SMAD3, FES, and PDGFRA) that modulate CAD risk through HCASMC, all of which have relevant functional roles in vascular remodeling. Comparison with GTEx data suggests that SIPA1 and PDGFRA influence CAD risk predominantly through HCASMC, while other annotated genes may have multiple cell and tissue targets. Together, these results provide new tissue-specific and mechanistic insights into the regulation of a critical vascular cell type associated with CAD in human populations.

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