PCSK9, A Promising Novel Target for Age-Related Cardiovascular Dysfunction

被引：9

作者：

Matyas, Csaba ^{[1
,2
]}

Trojnar, Eszter ^{[1
]}

Zhao, Suxian ^{[1
]}

Arif, Muhammad ^{[1
]}

Mukhopadhyay, Partha ^{[1
]}

Kovacs, Attila ^{[3
]}

Fabian, Alexandra ^{[3
]}

Tokodi, Marton ^{[3
]}

Bagyura, Zsolt ^{[3
]}

Merkely, Bela ^{[3
]}

Kohidai, Laszlo ^{[4
]}

Lajko, Eszter ^{[4
]}

Takacs, Angela ^{[4
]}

He, Yong ^{[5
]}

Gao, Bin ^{[5
]}

Paloczi, Janos ^{[1
]}

Lohoff, Falk W. ^{[6
]}

Hasko, Gyorgy ^{[7
]}

Ding, Wen-Xing ^{[8
,9
]}

Pacher, Pal ^{[1
,10
]}

机构：

[1] NIAAA, Lab Cardiovasc Physiol & Tissue Injury, NIH, Bethesda, MD USA

[2] Univ Pecs, Med Sch, Dept Med Imaging, Pecs, Hungary

[3] Semmelweis Univ, Heart & Vasc Ctr, Budapest, Hungary

[4] Semmelweis Univ, Dept Genet Cell & Immunobiol, Budapest, Hungary

[5] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA

[6] NIAAA, Sect Clin Genom & Expt Therapeut, NIH, Bethesda, MD USA

[7] Columbia Univ, Dept Anesthesiol, New York, NY USA

[8] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS USA

[9] Univ Kansas, Dept Internal Med, Med Ctr, Kansas City, KS USA

[10] NIAAA, Lab Cardiovasc Physiol & Tissue Injury, NIH, Bethesda, MD 20852 USA

来源：

JACC-BASIC TO TRANSLATIONAL SCIENCE | 2023年 / 8卷 / 10期

基金：

美国国家卫生研究院;

关键词：

cardiovascular aging; heart failure; NASH; nonalcoholic steatohepatitis; PCSK9; transcriptomics; SMOOTH-MUSCLE-CELLS; EXPRESSION; STRESS; ACCUMULATION; DISEASE; LDL;

D O I：

10.1016/j.jacbts.2023.06.005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 iden-tified 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.

引用

页码：1334 / 1353

页数：20

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