Atorvastatin prevents connexin43 remodeling in hypertrophied left ventricular myocardium of spontaneously hypertensive rats

Chen, Hong-Juan; Yao, Lihua; Chen, Tu-Gang; Min, Yu; Wang, Lihong; Chen, Jun-zhu

doi:10.1097/00029330-200711010-00010

Cited by 12 publications

(6 citation statements)

References 17 publications

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“…Hypertension and Hypertrophy. In spontaneously hypertensive rats, Cx43 protein expression either declines (Ba cová et al, 2012;Benova et al, 2013;Zhang et al, 2014) or increases (Chen et al, 2007;Zhao et al, 2008;Radosinska et al, 2013). The differences between the aforementioned studies may be due to the degree of left ventricular hypertrophy associated with hypertension, because in porcine and human myocardium Cx43 expression increases in the compensated phase but gradually decreases with the progression/decompensation of hypertrophy (Formigli et al, 2003;Kostin et al, 2004).…”

Section: B Cx43 and Risk Factors Of Cardiovascular Diseasesmentioning

confidence: 99%

Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications

Leybaert¹,

Lampe²,

Dhein³

et al. 2017

Pharmacol Rev

203

192

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Connexins are ubiquitous channel forming proteins that assemble as plasma membrane hemichannels and as intercellular gap junction channels that directly connect cells. In the heart, gap junction channels electrically connect myocytes and specialized conductive tissues to coordinate the atrial and ventricular contraction/relaxation cycles and pump function. In blood vessels, these channels facilitate long-distance endothelial cell communication, synchronize smooth muscle cell contraction, and support endothelial-smooth muscle cell communication. In the central nervous system they form cellular syncytia and coordinate neural function. Gap junction channels are normally open and hemichannels are normally closed, but pathologic conditions may restrict gap junction communication and promote hemichannel opening, thereby disturbing a delicate cellular communication balance. Until recently, most connexin-targeting agents exhibited little specificity and several off-target effects. Recent work with peptide-based approaches has demonstrated improved specificity and opened avenues for a more rational approach toward independently modulating the function of gap junctions and hemichannels. We here review the role of connexins and their channels in cardiovascular and neurovascular health and disease, focusing on crucial regulatory aspects and identification of potential targets to modify their function. We conclude that peptide-based investigations have raised several new opportunities for interfering with connexins and their channels that may soon allow preservation of gap junction communication, inhibition of hemichannel opening, and mitigation of inflammatory signaling.

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Section: B Cx43 and Risk Factors Of Cardiovascular Diseasesmentioning

confidence: 99%

Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications

Leybaert¹,

Lampe²,

Dhein³

et al. 2017

Pharmacol Rev

203

192

View full text Add to dashboard Cite

show abstract

“…Similarly in mice with aortic banding, total Cx43 expression remained unaltered but Cx43 became redistributed (Boulaksil et al, 2010) or total Cx43 expression decreased (Qu et al, 2009; Yasuno et al, 2013) and Cx43 was dephosphorylated (Yasuno et al, 2013). Indeed, many interventions which reduce hypertension and/or hypertrophy (angiotensin II (AT) receptor 1-blockade(Zhao et al, 2008) or knockout (Yasuno et al, 2013), aldosterone antagonists (Yasuno et al, 2013), renin inhibition (Zhang et al, 2014) but also compounds such as melatonin (Benova et al, 2013), atorvastatin (Bacova et al, 2010; Chen et al, 2007), omega-3 free fatty acids (Bacova et al, 2012) or red palm oil (Mitasikova et al, 2008)) attenuate the observed changes in Cx43 expression and/or phosphorylation. Interestingly, blockade of AT- receptor 1 attenuated microRNA-1 expression (Curcio et al, 2013) which subsequently affected Cx43 expression: an increase in microRNA-1 secondary to p38MAPK activation in cardiomyocytes (Zhang et al, 2010b) or overexpression of microRNA-1 in mice depressed Cx43 expression (Zhang et al, 2010b) but a decrease in microRNA-1 increased Cx43 expression in female hearts (Stauffer et al, 2011).…”

Section: Cx43 Function In the Presence Of Major Cardiovascular Rismentioning

confidence: 99%

Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection

Schulz

Görge

Görbe

et al. 2015

Pharmacology & Therapeutics

202

174

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Connexins are widely distributed proteins in the body that are crucially important for heart and brain function. Six connexin subunits form a connexon or hemichannel in the plasma membrane. Interactions between two hemichannels in a head-to-head arrangement result in the formation of a gap junction channel. Gap junctions are necessary to coordinate cell function by passing electrical current flow between heart and nerve cells or by allowing exchange of chemical signals and energy substrates. Apart from its localisation at the sarcolemma of cardiomyocytes and brain cells, connexins are also found in mitochondria where they are involved in the regulation of mitochondrial matrix ion fluxes and respiration. Connexin expression is affected by age and gender as well as several pathophysiological alterations such as hypertension, hypertrophy, diabetes, hypercholesterolemia, ischemia, post-myocardial infarction remodelling or heart failure, and post-translationally connexins are modified by phosphorylation/de-phosphorylation and nitros(yl)ation which can modulate channel activity. Using knockout/knockin technology as well as pharmacological approaches, one of the connexins, namely connexin 43, has been identified to be important for cardiac and brain ischemia/reperfusion injury as well as protection from it. Therefore, the current review will focus on the importance of connexin 43 for irreversible injury of heart and brain tissue following ischemia/reperfusion and will highlight the importance of connexin 43 as an emerging therapeutic target in cardio- and neuroprotection.

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“…Caduet is a single pill containing a combination of amlodipine besylate and atorvastatin calcium tablet (AM + AT), which is widely used in the clinical treatment of cardiovascular diseases, such as hypertension and coronary heart disease (8). In addition, previous experimental and clinical studies have reported that AM + AT can prevent cardiac hypertrophy and remodeling (9,10).…”

Section: Introductionmentioning

confidence: 99%

“…Connexin 43 (Cx43)-associated GJ protein in ventricular cardiomyocytes and vascular smooth muscle cells is involved in cardiac and vascular remodeling (13). Moreover, left ventricular remodeling is closely associated with the expression and distribution of Cx43 in cardiomyocytes (9,14), and our previous study revealed that the expression of Cx43 was enhanced in the thoracic aorta of SH model rats (SHR) (15). Previous studies have also reported that Cx43 XIAOYAN HUANG 1 , JUNLU YANG 2 , BAOGUO SONG 3 , NANA WANG 1 , MEIJUAN MA 4 , HAIFANG WANG 5 , SHA WANG 3 , SHUANGPING HAO 6 and GONG CHENG 4 phosphorylation contributes to ischemia-associated remodeling of Cx43 channels in cardiomyocytes (16,17), and Cx43 dephosphorylation contributes to arrhythmias and cardiomyocyte apoptosis in ischemia/reperfusion hearts (18).…”

Section: Introductionmentioning

confidence: 99%

Caduet enhances connexin 43 phosphorylation in left ventricular and thoracic aorta of SH model rats

Huang

Yang²,

Song

et al. 2020

Exp Ther Med

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; subsequently, body weight, heart rate (HR), left ventricular mass index (LVMI), blood pressure (BP), plasma lipid levels and morphological changes of myocardial tissue in each group were analyzed. The expression of total (T)-Cx43 and phosphorylated (P)-Cx43 protein in the left ventricular and thoracic aortic tissues was determined using western blotting and immunofluorescence double labeling. The results revealed that AM + AT significantly decreased LVMI and cardiomyocyte cross-sectional area compared with SHR-AM and SHR-AT group. The western blotting results demonstrated that AM + AT could inhibit the expression of T-Cx43 protein, but increased the expression of P-Cx43 in the left ventricular and thoracic aorta. Moreover, immunofluorescence results indicated AM + AT could also decrease the expression T-Cx43, and increase that of P-Cx43 in the left ventricular and thoracic aorta compared with AM and AT alone. Therefore, it was concluded that AM + AT may mitigate left ventricular and thoracic aorta remodeling in SH rats by enhancing Cx43 phosphorylation, and the efficacy of AM + AT was superior to that of AM and AT alone.

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Atorvastatin prevents connexin43 remodeling in hypertrophied left ventricular myocardium of spontaneously hypertensive rats

Cited by 12 publications

References 17 publications

Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications

Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications

Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection

Caduet enhances connexin 43 phosphorylation in left ventricular and thoracic aorta of SH model rats

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