Mice with Double Knockout of Calponin 1 and Calponin 2 Genes Demonstrate Contractility Modifications in Vascular Smooth Muscle

Calponin is an actin filament associated regulatory protein in smooth muscle and non-muscle cells. Calponin-1 is specifically expressed in smooth muscle cells and calponin-2 is expressed in both smooth muscle and multiple non-muscle cell types. The role of calponin-1 in the regulation of smooth muscle contraction has been extensively investigated. Calponin-1 gene knockout mice demonstrated minor but clearly detectable changes in smooth muscle contractility, especially in the urogenital system. Here we compared the impacts of single and double knockout of calponin-1 and calponin-2 genes in mice on smooth muscle contractility. The results showed that either calponin-1 or calponin-2 knockout did not significantly alter the passive tension-active tension relationship in aortic smooth muscle and the mice exhibited normal blood pressure. The double knockout mice survived well into adulthood in the absence of physiological stress. However, the double knockout mice showed higher passive tension and less KCl- and norepinephrine-induced active tension in endothelium-removed aorta rings. The double knockout mice also showed lower systolic and diastolic blood pressures compared to gender-matched wild type controls. The results suggest that calponin-1 and −2 both contribute to the regulation of vascular smooth muscle contractility. The minimized phenotypic effects of calponin-1 and calponin-2 single knockout mice indicate a mutual compensation between the two isoforms in smooth muscle cells. Supporting this notion, analysis of protein expression in various types of smooth muscle showed up-regulations of one isoform when the other was deleted. The results implicate that calponins are molecular targets for modifications of smooth muscle contractility and especially blood pressure. Simultaneously targeting the expression and function of both two calponins may provide a potential therapeutic approach to the development of new treatment of hypertension.