Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 141, Issue 2, Pages 308-315Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2020.05.115
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Funding
- National Institutes of Health (Bethesda, MD) [T32HL098129]
- National Institutes of Health Clinical and Translational Science Awards at New Youth University Awards (New York, NY) [UL1TR001445, KL2TR001446, TL1TR001447]
- American Heart Association Career Development Grant (Dallas, TX) [18CDA34080540, 18CDA34110203AHA]
- Dermatology Foundation Research Award
- National Psoriasis Foundation
- American Society of Hematology [18-A0-00-1001884]
- National Institutes of Health [ZIA-HL-06193-06, ZIA-HL-06235-02, R01HL139909, R01HL114978, R35HL144993]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZIAHL006193, ZIAHL006220, ZIAHL006235] Funding Source: NIH RePORTER
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The study found that PCSK9 levels were elevated in psoriasis patients, correlated with disease severity, and associated with cardiovascular risk factors in both animal models and human cohorts.
Mechanisms explaining the link between psoriasis, a proinflammatory condition, and cardiovascular disease are not fully known. PCSK9 is predominantly expressed in hepatocytes as a critical regulator of lipid metabolism, and clinical trials targeting PCSK9 reduce cardiovascular disease. Independent of its role in lipid metabolism, PCSK9 levels associate with endothelial dysfunction and predict cardiovascular events. We used two separate human psoriasis cohorts and the K14-Rac1V12(-/+) murine model of psoriasis to investigate PCSK9 and cardiovascular risk in psoriasis. In both psoriasis cohorts (n = 88 and n = 20), PCSK9 levels were 20% and 13% higher than in age-, sex-, and cholesterol-matched controls, respectively (P < 0.05 for each comparison) and correlated with PASI (r = 0.43, P < 0.05). Despite no difference in hepatocyte expression, K14-Rac1V12(-/+) mice demonstrated skin-specific PCSK9 staining, which was confirmed in human psoriatic lesional skin. In patients with psoriasis, PCSK9 levels correlated with impaired endothelial vascular health (e.g., early atherosclerosis, beta = 4.5, P < 0.01) and log converted coronary artery calcium score (beta = 0.30, P = 0.01), which remained significant after adjustment for Framingham risk, body mass index, and active biologic use. Taken together, these findings suggest, independent of cholesterol, an association between circulating PCSK9 and early as well as advanced stages of atherosclerosis in psoriasis.
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