PCSK9, A Promising Novel Target for Age-Related Cardiovascular Dysfunction
Csaba Mátyás, Eszter Trojnár, Suxian Zhao, Muhammad Arif, Partha Mukhopadhyay, Attila Kovács, Alexandra Fábián, Márton Tokodi, Zsolt Bagyura, Béla Merkely, László Kőhidai, Eszter Lajkó, Angéla Takács, Yong He, Bin Gao, János Pálóczi, Falk W. Lohoff, György Haskó, Wen‐Xing Ding, Pál Pacher
Abstract
Cardiovascular diseases (CVDs) 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, blood PCSK9 level correlated positively with increasing age and the development of cardiovascular dysfunction. Age-related fatty degeneration of liver tissue positively correlated with serum PCSK9 levels in the rat model, while development of age-related nonalcoholic fatty liver disease correlated with cardiovascular functional impairment. 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.