PCSK9, a promising novel target for age-related cardiovascular dysfunction

Cardiovascular diseases (CVD) are the leading cause of death among elderly people. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important regulator of cholesterol metabolism. Herein, we investigated the role of PCSK9 in age-related CVD. Both in humans and rats, sPCSK9 correlated positively with increasing age and the development of cardiovascular dysfunction. Network analysis identified PCSK9 as an important factor in age-associated lipid alterations and it correlated positively with intima media thickness, a clinical parameter of CVD risk. PCSK9 inhibition with alirocumab effectively reduced the CVD progression in aging rats suggesting that PCSK9 plays an important role in cardiovascular aging. Overall design: A population-based screening program and the iNetModels database were used to explore the PCSK9's role in cardiovascular aging in humans. A rat model of advanced aging was applied to study age-related cardiovascular/hepatic changes and to investigate the effects of PCSK9 inhibition on cardiovascular aging.