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Intimal calcification is the formation of mineralised tissue within atherosclerotic lesions and can lead to an increased risk of plaque rupture and mortality in man. Even though experimental data are sparse, it had been suggested that inhibiting protein kinase Cα (PKCα) may be of therapeutic benefit in atherosclerosis. However, we recently discovered that loss of PKCα increases mineral deposition by vascular smooth muscle cells (VSMCs) in a transforming growth factor-β (TGFβ)-dependent manner in vitro, suggesting that vascular calcification and its devastating consequences could be increased if patients with cardiovascular disease are treated with PKCα inhibitors. This study tests the hypothesis that PKCα regulates atherosclerosis and intimal calcification in vivo. Nine to ten week-old male PKCα knock-out (PKCα-/-) mice crossed with ApoE-/- mice (PKCα-/-ApoE-/-) were fed a high-fat, high-cholesterol diet (Western diet) for 8, 18 and 28 weeks. Male ApoE-/- mice fed the same diet were used as controls. En face Oil Red O staining was significantly increased (∼1.5-fold, P Aortic sinus lesion size was not significantly different between PKCα-/-ApoE-/- and ApoE-/- mice at any time point. However, a significant increase in intimal calcification (∼2-fold, P In conclusion, our study has identified that PKCα may play a protective role in both atherosclerosis and intimal calcification. This suggests that inhibiting PKCα may not be of any therapeutic benefit in atherosclerosis. Activation of PKCα could instead represent a new therapeutic target for atherosclerosis-induced intimal calcification. Conflict of interest None |
