Atorvastatin prevents connexin43 remodeling in hypertrophied left ventricular myocardium of spontaneously hypertensive rats.
BACKGROUND
Connexin43 (Cx43) is the predominant gap junction protein in heart and is involved in the control of cell-to-cell communication to modulate the contractility and the electrical coupling of cardiac myocytes. Left ventricular (LV) hypertrophy is accompanied by changes of Cx43 expression. Recent studies have demonstrated that statins reduced cardiac hypertrophy. However, it is unknown whether statins can affect Cx43 expression in hypertrophied left ventricular myocardium. This study was designed to assess the effects of atorvastatin on LV hypertrophy and Cx43 expression in spontaneously hypertensive rats (SHR).


METHODS
Nine-week old SHRs were randomly divided into two groups. Some received atorvastatin at 30 mg/kg by oral gavage once daily for 8 weeks (SHR-A); others received vehicle. Age-matched Wistar-Kyoto rats (WKY) received atorvastatin or vehicle for 8 weeks were used as controls. At the end of the experiment, we investigated LV hypertrophy and the expression of Cx43 in LV myocardium in four groups. Cx43 expression was investigated by the methods of Western blotting, immunohistochemistry, and transmission electron microscope. LV hypertrophy was accessed by pathological analysis and plasma brain natriuretic peptide (BNP) level.


RESULTS
LV hypertrophy was prominent in untreated SHR. In SHR, LV myocardium Cx43 level was upregulated, and the distribution of Cx43 was displaced from their usual locations to other sites at various distances away from the intercalated disks. After atorvastatin treatment, myocardium Cx43 level was reduced in SHR-A, and the distribution of Cx43 gap junction became much regular and confined to intercalated disk. Statins also prevented LV hypertrophy in SHR.


CONCLUSIONS
These results provide novel in vivo evidence for the key role of Cx43 gap junctions in LV hypertrophy and the possible mechanism in anti-hypertrophic effect of statins. Atorvastatin treatment may have beneficial effects on LV hypertrophy in spontaneously hypertensive rats.
Chen
Hong-juan
HJ
Department of Cardiology, First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, China.
Yao
Lei
L
Chen
Tu-gang
TG
Yu
Min
M
Wang
Li-hong
LH
Chen
Jun-zhu
JZ
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D018031:Connexin 43 / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000924:Anticholesteremic Agents; D018031:Connexin 43; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D020097:Natriuretic Peptide, Brain; D000069059:Atorvastatin