Role of PAI-1 in hepatic steatosis and dyslipidemia

被引：51

作者：

Levine, Joshua A. ^{[1
]}

Oleaga, Carlota ^{[2
]}

Eren, Mesut ^{[1
]}

Amaral, Ansel P. ^{[1
]}

Shang, Meng ^{[1
]}

Lux, Elizabeth ^{[1
]}

Khan, Sadiya S. ^{[1
]}

Shah, Sanjiv J. ^{[1
]}

Omura, Yasuhiro ^{[1
]}

Pamir, Nathalie ^{[2
]}

Hay, Joshua ^{[2
]}

Barish, Grant ^{[1
,3
]}

Miyata, Toshio ^{[4
]}

Tavori, Hagai ^{[2
]}

Fazio, Sergio ^{[2
]}

Vaughan, Douglas E. ^{[1
]}

机构：

[1] Northwestern Univ, Dept Med, Feinberg Sch Med, Arkes Pavil,Suite 2330,676 N St,Clair St, Chicago, IL 60611 USA

[2] Oregon Hlth & Sci Univ, Ctr Prevent Cardiol, Knight Cardiovasc Inst, Portland, OR 97201 USA

[3] Jesse Brown VA Med Ctr, Dept Med, Chicago, IL USA

[4] Tohoku Univ, Dept Mol Med & Therapy, United Ctr Adv Res & Translat Med, Grad Sch Med, Sendai, Miyagi, Japan

来源：

SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期

关键词：

PLASMINOGEN-ACTIVATOR INHIBITOR-1; METABOLIC SYNDROME; PCSK9; OBESITY; CHOLESTEROL; DISEASE; PROTECTS; TM5441; LDLR;

D O I：

10.1038/s41598-020-79948-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Plasminogen activator inhibitor 1 (PAI-1) is a functional biomarker of the metabolic syndrome. Previous studies have demonstrated that PAI-1 is a mechanistic contributor to several elements of the syndrome, including obesity, hypertension and insulin resistance. Here we show that PAI-1 is also a critical regulator of hepatic lipid metabolism. RNA sequencing revealed that PAI-1 directly regulates the transcriptional expression of numerous genes involved in mammalian lipid homeostasis, including PCSK9 and FGF21. Pharmacologic or genetic reductions in plasma PAI-1 activity ameliorates hyperlipidemia in vivo. These experimental findings are complemented with the observation that genetic deficiency of PAI-1 is associated with reduced plasma PCSK9 levels in humans. Taken together, our findings identify PAI-1 as a novel contributor to mammalian lipid metabolism and provides a fundamental mechanistic insight into the pathogenesis of one of the most pervasive medical problems worldwide.

引用

页数：13

共 41 条

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