TITLE:
Pharmacological Effects of Statins Related to Gap Junction Modulation
AUTHORS:
Lili Qu, Jiandong Jiang, Weijia Kong
KEYWORDS:
Statin; Connexin; Gap Junction; Atherosclerosis; Arrhythmia; Bystander Effect
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.5 No.4,
April
9,
2014
ABSTRACT: 3-Hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitors, or “statins”, are widely using cholesterol-lowering
drugs with pleiotropic pharmacological effects. In this review, we summarized the
pharmacological effects of statins related to gap junction modulation. The main
function of cellular gap junctions, which are composed of trans-membrane proteins
named connexins (Cxs), is to mediate direct cell-to-cell communication through material
exchange. Statins could rectify the disturbed expression, distribution, or phosphorylation
of Cxs and thus modify the functions of gap junctions in a variety of tissues like
the aorta, cardiomyocytes, or tumors. The effects of statins on Cxs and gap junctions
were associated with their pharmacological activities against atherosclerosis, arrhythmias,
and tumors. Despite some evidences suggested that the anti-inflammatory or HMG-CoA
reductase inhibiting effects of statins may contribute in part to the modulation
of Cxs and gap junctions, the detailed underlying mechanisms are largely unrevealed
and merit further investigation. In addition, it is likely that the modulating effects
of statins on gap junctions may also contribute to their pharmacological activities
against some diabetic complications. Future studies of these issues will help to
provide scientific evidences for the appropriate clinical application of statins.