<i>Cx37</i>C1019T Polymorphism May Contribute to the Pathogenesis of Coronary Heart Disease

Zhao, Long; Liu, Ying; Wu, Di; Ma, Tao; Xia, Shunren; Li, Zhi

doi:10.1089/gtmb.2014.0034

Cited by 7 publications

(3 citation statements)

References 28 publications

(36 reference statements)

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“…The overall odds ratios (OR) and 95% confidence intervals (95% CI) were 1.04, 0.95-1.15; and 1.02, 0.85-1.22 in dominant and recessive models, respectively. Another meta-analysis aiming at evaluating the role of C1019T in the pathogenesis of CHD was conducted by Zhao and his colleagues [100]. They included 9 case-control studies with a total of 1426 CHD cases and 929 controls and calculated the ORs and their 95% CIs.…”

Section: A Gja4 (Cx37) Polymorphism and Non-structural Afmentioning

confidence: 99%

Atrial Fibrillation: Focus on Myocardial Connexins and Gap Junctions

Guo

Yang

2022

Biology

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Atrial fibrillation (AF) represents the most common type of clinical cardiac arrhythmia worldwide and contributes to substantial morbidity, mortality and socioeconomic burden. Aggregating evidence highlights the strong genetic basis of AF. In addition to chromosomal abnormalities, pathogenic mutations in over 50 genes have been causally linked to AF, of which the majority encode ion channels, cardiac structural proteins, transcription factors and gap junction channels. In the heart, gap junctions comprised of connexins (Cxs) form intercellular pathways responsible for electrical coupling and rapid coordinated action potential propagation between adjacent cardiomyocytes. Among the 21 isoforms of connexins already identified in the mammal genomes, 5 isoforms (Cx37, Cx40, Cx43, Cx45 and Cx46) are expressed in human heart. Abnormal electrical coupling between cardiomyocytes caused by structural remodeling of gap junction channels (alterations in connexin distribution and protein levels) has been associated with enhanced susceptibility to AF and recent studies have revealed multiple causative mutations or polymorphisms in 4 isoforms of connexins predisposing to AF. In this review, an overview of the genetics of AF is made, with a focus on the roles of mutant myocardial connexins and gap junctions in the pathogenesis of AF, to underscore the hypothesis that cardiac connexins are a major molecular target in the management of AF.

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Section: A Gja4 (Cx37) Polymorphism and Non-structural Afmentioning

confidence: 99%

Atrial Fibrillation: Focus on Myocardial Connexins and Gap Junctions

Guo

Yang

2022

Biology

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“…Cx37 is increasingly understood to be a potent regulator of vessel stability and growth [7, 10, 12], and its dysfunction is implicated in cardiovascular diseases involving vessel malformation [38, 49], vessel wall hyperplasia [95], as well as immune cell responses in atherosclerosis [16]. Polymorphic variation in the Cx37 gene that alters the protein’s amino acid sequence at site 319 in the Cx37 C-terminus is well established to influence risk for cardiovascular disease in healthy and diabetic patients [78, 80, 81, 96]. Thus, Cx37 is a potentially attractive target in the pursuit of novel therapies to address blood vessel disorganization and overgrowth, as well as other forms of cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the Cx37 319 residue is polymorphic in humans with either proline (Cx37-1019C) or serine (Cx37-1019T) residues present at high frequency within the general population [77][78][79][80][81]. The Cx37-1019C (Cx37-P319) variant -which presumably cannot be phosphorylated at the 319 site (but could be phosphorylated at nearby sites) -is strongly associated with increased risk for cardiovascular disease [78,80,81] and breast cancer [46]. Yet, in vitro studies in HeLa or SK-Hep-1 cancer cells find that Cx37-P319 -not Cx37-S319 -is growth suppressive [55].…”

Section: Phosphorylation Of Cx37 Likely Induces a Closed Channel Conf...mentioning

confidence: 99%

Connexin37 Regulates Cell Cycle in the Vasculature

Fang

Burt

2022

J Vasc Res

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Control of vascular cell growth responses is critical for development and maintenance of a healthy vasculature. Connexins – the proteins comprising gap junction channels – are key regulators of cell growth in diseases such as cancer, but their involvement in controlling cell growth in the vasculature is less well appreciated. Connexin37 (Cx37) is one of four connexin isotypes expressed in the vessel wall. Its primary role in blood vessels relies on its unique ability to transduce flow-sensitive signals into changes in cell cycle status of endothelial (and perhaps, mural) cells. Here, we review available evidence for Cx37’s role in the regulation of vascular growth, vessel organization, and vascular tone in healthy and diseased vasculature. We propose a novel mechanism whereby Cx37 accomplishes this with a phosphorylation-dependent transition between closed (growth-suppressive) and multiple open (growth-permissive) channel conformations that result from interactions of the C-terminus with cell-cycle regulators to limit or support cell cycle progression. Lastly, we discuss Cx37 and its downstream signaling as a novel potential target in the treatment of cardiovascular disease, and we address outstanding research questions that still challenge the development of such therapies.

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