scholarly journals Association of the 1q25 Diabetes-Specific Coronary Heart Disease Locus With Alterations of the γ-Glutamyl Cycle and Increased Methylglyoxal Levels in Endothelial Cells

Diabetes ◽  
2020 ◽  
Vol 69 (10) ◽  
pp. 2206-2216
Author(s):  
Caterina Pipino ◽  
Hetal Shah ◽  
Sabrina Prudente ◽  
Natalia Di Pietro ◽  
Lixia Zeng ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Disease Locus

P-055 The circulating endothelial cells level and coronary heart disease in women

2013 ◽  
Vol 131 ◽  
pp. S91
Author(s):  
O. Sirotkina ◽  
V. Feoktistova ◽  
A. Laskovets ◽  
I. Leonova ◽  
L. Gaykovaya ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Circulating Endothelial Cells

scholarly journals Disease-Related Growth Factor and Embryonic Signaling Pathways Modulate an Enhancer of TCF21 Expression at the 6q23.2 Coronary Heart Disease Locus

PLoS Genetics ◽  
2013 ◽  
Vol 9 (7) ◽  
pp. e1003652 ◽  
Author(s):  
Clint L. Miller ◽  
D. Ryan Anderson ◽  
Ramendra K. Kundu ◽  
Azad Raiesdana ◽  
Sylvia T. Nürnberg ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Disease Locus ◽  
Embryonic Signaling

Polymorphisms in the P-selectin (CD62P) and P-selectin glycoprotein ligand-1 (PSGL-1) genes and coronary heart disease

2004 ◽  
Vol 42 (9) ◽  
Author(s):  
Peter Bugert ◽  
Marion Vosberg ◽  
Mathias Entelmann ◽  
Jürgen Jahn ◽  
Hugo A. Katus ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Coding Regions

AbstractP-selectin and its ligand, PSGL-1, are cell adhesion molecules that facilitate interaction of platelets, leukocytes and endothelial cells. Polymorphisms of these genes have been reported to be associated with coronary heart disease (CHD). In the present study, we characterized the entire coding regions of

Therapeutic Angiogenesis in Ischemic Heart Disease

1999 ◽  
Vol 82 (08) ◽  
pp. 772-780 ◽  
Author(s):  
Armin Helisch ◽  
J. Anthony Ware
Keyword(s):  
Coronary Heart Disease ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Growth Factors ◽  
Endothelial Cell ◽  
Vascular Disease ◽  
Endothelial Cell Proliferation ◽  
Mechanical Factors ◽  
Collateral Vessels

IntroductionCoronary heart disease is the leading cause of death in the Western world. Traditionally, patients with coronary heart disease requiring a revascularizing procedure have had to undergo either coronary artery bypass surgery, which usually involves open thoracotomy, or percutaneous transluminal balloon angioplasty, or a related procedure. Unfortunately, especially in patients with severe diffuse coronary heart disease, revascularization by these means can be difficult or even impossible. It has been shown that incomplete revascularization is a predictor of a worsened postoperative outcome (i.e., recurrent angina, myocardial infarction, or even death).We have known for a long time that many patients with ischemic disease develop angiographically visible collateral vessels. Initial research focused on the enlargement of preexisting collateral vessels, a process for which Wolfgang Schaper has proposed the term “neoarteriogenesis.”1 It is now clear that true “angiogenesis,” defined as the formation of new vessels by sprouting from preexisting vessels, also occurs. The latter also should be differentiated from the earliest embryological process of new vessel formation directly from mesodermal endothelial cell precursors, which is called “vasculogenesis.”2 In the last few years, clinical trials have been initiated with the goal of enhancing angiogenesis to treat peripheral vascular disease and ischemic heart disease. In this review, we will summarize the underlying concepts for this novel mode of therapy, plus the available information on its efficacy.The sprouting of capillaries from preexisting vessels (angiogenesis) is a normal and necessary process to supply the growing organism with nutrients and oxygen. Ischemic vascular disease, along with wound healing and the monthly endometrial proliferation, are conditions in which angiogenesis may be beneficial or necessary. Of course, angiogenesis is also part of the pathogenic mechanism of tumors, hemangiomas, proliferative retinopathies, and inflammatory diseases like rheumatoid arthritis and psoriasis.3 Even in ischemic vascular disease, it is possible that vascularization of atherosclerotic plaques by vessels arising from the vasa vasorum leads to hemorrhages with consequent plaque instability,4 and thus enhancing angiogenesis may promote vessel pathology.The vasculature of a 70 kg adult is lined by approximately 1,000 m2 of quiescent endothelial cells with a very low turnover rate that can exceed 1,000 days.3 Upon angiogenic activation (e.g., by growth factors released during ischemia), a local inflammatory reaction often can be observed with increased local vascular permeability, vasodilation, and accumulation of monocytes and macrophages. These latter cells release more cytokines and growth factors, which lead to the accumulation of additional inflammatory cells. They also release enzymes that promote the proteolytic degradation of the underlying extracellular matrix and basal membrane. Such degradation causes the endothelial cells to detach from their neighboring cells and the underlying matrix, followed by chemotactic migration and proliferation. Subsequently, formation of a lumen occurs and, eventually, maturation and growth of the newly formed vessel.2,5,6 In vessels larger than capillaries, vascular smooth muscle cells proliferate and migrate as well. In addition, it recently has been shown that circulating endothelial cell precursors released from the bone marrow participate in the formation of new vessels in the setting of tissue ischemia.7 Investigators currently are assessing the importance and contribution of the latter mechanism to neovascularization in the adult organism. If it proves substantial, the traditional means of differentiating between angiogenesis and vasculogenesis may need to be reconsidered.The regulatory mechanisms of angiogenesis are very complex and only partially understood. Both mechanical factors and multiple endogenous inhibitors have been identified that probably act to inhibit inappropriate endothelial cell proliferation following mitogenic stimulation.3 Most of the known angiogenesis inhibitors circulate in the blood and some have been detected in the matrix around endothelial cells. They include platelet factor 4, thrombospondin-1 and -2, tissue inhibitors of metalloproteinases, and interferon α.3,8 It is unclear whether the endothelium specific inhibitors angiostatin, a 38 kDa fragment of plasminogen,3 and endostatin, a 20 kDa fragment of collagen XVIII,9 are present in physiologically active amounts in organisms without malignant tumors. Of potential importance for myocardial angiogenesis is the recent isolation of an 11 kDa inhibitor of endothelial and smooth muscle proliferation and angiogenesis with homology to the B-cell translocator gene (btg-1) from the bovine heart.1,10 Regarding mechanical factors, contact inhibition of endothelial cell proliferation, which easily can be observed by growing primary endothelial cells in a culture dish, limits excessive endothelial cell growth. Additionally, endothelial cells are surrounded in vivo by a basal lamina, which creates a physical barrier between endothelial cells and the extravascular space. Pericytes may regulate or restrain endothelial cell proliferation. Angiogenesis also can be inhibited by sequestration of angiogenic factors in the extracellular matrix; furthermore, changes of endothelial cell shape may decrease their sensitivity to growth factors.3 On the other hand, many endogenous factors that promote angiogenesis have been identified. These include various growth factors that interact with receptor tyrosine kinases (see below), angiogenin, granulocyte colony stimulating factor, interleukin-8, and proliferin.3,11,12 The balance of these inhibitory and mitogenic influences determines whether angiogenesis occurs.

scholarly journals Long Noncoding RNA EZR-AS1 Regulates the Proliferation, Migration, and Apoptosis of Human Venous Endothelial Cells via SMYD3

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ganhua You ◽  
Xiangshu Long ◽  
Fang Song ◽  
Jing Huang ◽  
Maobo Tian ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Antisense Rna ◽  
Noncoding Rna ◽  
Opposite Effect ◽  
Histone H3 ◽  
Noncoding Rnas

Numerous studies have shown that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of human cardiovascular diseases. However, whether lncRNA ezrin antisense RNA 1 (EZR-AS1) is associated with the progression of coronary heart disease (CHD) remains unclear. Accordingly, the aim of the present study was to evaluate the role of lncRNA EZR-AS1 in patients with CHD and in human venous endothelial cells (HUVECs). The findings revealed that lncRNA EZR-AS1 was highly expressed in the peripheral blood of patients with CHD. In vitro experiments showed that the overexpression of EZR-AS1 could enhance proliferation, migration, and apoptosis by upregulating the expression of EZR in HUVECs; downregulation of lncRNA EZR-AS1 resulted in the opposite effect. lncRNA EZR-AS1 was also found to regulate SET and MYND domain-containing protein 3 (SMYD3), a histone H3 lysine 4-specific methyltransferase, which subsequently mediated EZR transcription. Collectively, these results demonstrate that lncRNA EZR-AS1 plays an important role in HUVECs function via SMYD3 signaling.

scholarly journals Association of the 1q25 diabetes-specific coronary heart disease locus with alterations of the γ-glutamyl cycle and increased methylglyoxal levels in endothelial cells

2020 ◽  
Author(s):  
Ada Admin ◽  
Caterina Pipino ◽  
Hetal Shah ◽  
Sabrina Prudente ◽  
Natalia Di Pietro ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Glutamic Acid ◽  
Risk Allele ◽  
Umbilical Vein ◽  
Glutamine Supplementation ◽  
Chd Risk ◽  
Umbilical Vein Endothelial Cells

A chromosome 1q25 variant (rs10911021) has been associated with coronary heart disease (CHD) in type 2 diabetes (T2D). In human umbilical vein endothelial cells (HUVECs), the risk allele ‘C’ is associated with lower expression of the adjacent gene <i>GLUL</i> encoding glutamine synthase, converting glutamic acid to glutamine. To further investigate the mechanisms through which this locus affects CHD risk, we measured 35 intracellular metabolites involved in glutamic acid metabolism and g-glutamyl cycle in 62 HUVEC strains carrying different rs10911021 genotypes. Eight metabolites were positively associated with the risk allele (17%-58% increase/allele copy, p=0.046-0.002), including five g-glutamyl amino acids, b-citryl-glutamate, N-acetyl-aspartyl-glutamate, and ophthalmate - a marker of g-glutamyl cycle malfunction. Consistent with these findings, the risk allele was also associated with decreased glutathione/glutamate ratio (-9%, p=0.012), decreased S-lactoylglutathione (-41%, p=0.019), and reduced detoxification of the atherogenic compound methylglyoxal (+54%, p=0.008). <i>GLUL</i> down-regulation by shRNA caused a 40% increase in methylglyoxal level, which was completely prevented by glutamine supplementation. In summary, we have identified intracellular metabolic traits associated with the 1q25 risk allele in HUVECs, including impairments of the g-glutamyl cycle and methylglyoxal detoxification. Glutamine supplementation abolishes the latter abnormality, suggesting that such treatment may prevent CHD in 1q25 risk allele carriers.

scholarly journals The VEGFA156b isoform is dysregulated in senescent endothelial cells and may be associated with prevalent and incident coronary heart disease

2018 ◽  
Vol 132 (3) ◽  
pp. 313-325 ◽  
Author(s):  
Eva Latorre ◽  
Luke C. Pilling ◽  
Benjamin P. Lee ◽  
Stefania Bandinelli ◽  
David Melzer ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Peripheral Blood ◽  
Cell Types ◽  
Splicing Factor ◽  
Factor Expression ◽  
Endothelial Genes ◽  
Splicing Patterns ◽  
Peripheral Blood Leucocytes

Coronary heart disease (CHD) is a leading cause of morbidity in people over 65 years of age; >40% of all deaths are due to this condition. The association between increasing age and CHD is well documented; the accumulation of senescent cells in cardiac and vascular tissues may represent one factor underpinning this observation. We aimed to identify senescence-related expression changes in primary human senescent cardiomyocytes and endothelial cells and to relate transcript expression in peripheral blood leucocytes to prevalent and incident CHD in the InCHIANTI study of aging. We quantified splicing factor expression and splicing patterns of candidate transcripts in proliferative and senescent later passage endothelial cells and cardiomyocytes using qRTPCR. Senescence-associated isoforms also expressed in peripheral blood leucocytes were then examined for associations with CHD status in 134 pairs of age, sex and BMI-matched CHD cases and controls. Splicing factor expression was dysregulated in senescent cardiomyocytes, as previously reported for endothelial cells, as was the expression of alternatively expressed cardiac and vascular candidate genes in both cell types. We found nominal associations between the expression of VEGFA156b and FNI-EIIIIA isoforms in peripheral blood mRNA and CHD status. Dysregulated splicing factor expression is a key feature of senescent cardiomyocytes and endothelial cells. Altered splicing of key cardiac or endothelial genes may contribute to the risk of CHD in the human population.

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