School of Medicine and Health Sciences Poster Presentations

Title

Skin-specific expression of PCSK9 may provide novel link for increased cardiovascular disease risk in psoriasis

Poster Number

144

Document Type

Poster

Status

Medical Student

Abstract Category

Cardiology/Cardiovascular Research

Keywords

psoriasis, cardiovascular, pcsk9, ldlr

Publication Date

Spring 2018

Abstract

Cardiovascular disease (CVD) remains the most common cause of death worldwide and is more prevalent in chronic inflammatory states such as psoriasis. Recently, pro-protein convertase subtilisin/kexin type 9 (PCSK9) has gained attention as a novel therapeutic target in CVD due to its LDL cholesterol lowering capabilities. Therefore, we sought to investigate the relationship between PCSK9 and psoriasis. In patients with psoriasis (n=88), circulating PCSK9 levels are elevated compared to those of healthy volunteers (HV) (n=52) (Psoriasis: 253 ng/mL vs HV: 189 ng/mL, p<0.001) and are positively associated with coronary artery calcium (CAC) scores, beyond traditional cardiovascular risk factors (β =0.38, p<0.004).

Similarly, in our mouse model of psoriasis, we observe a 1.7-fold increase (p<0.0001) in circulating PCSK9 compared to that of littermate controls. Moreover, there is a robust relationship between circulating PCSK9 levels and psoriasis skin severity (β =0.92, p<0.001). We also find that although hepatic PCSK9 protein levels are unchanged in the psoriatic mice, low-density lipoprotein receptor (LDLR), the direct target of PCSK9, is significantly decreased at the protein level. Furthermore, we determine that both PCSK9 mRNA and protein levels are elevated in the lesional skin of psoriatic mice compared to those of littermate controls, a finding we confirmed in our psoriatic human skins. Taken together, we postulate that psoriatic lesional skin, specifically the epidermis, is the source for elevated plasma PCSK9, thereby decreasing hepatic LDLR, and suggesting a potential link between psoriasis and cardiovascular disease.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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Skin-specific expression of PCSK9 may provide novel link for increased cardiovascular disease risk in psoriasis

Cardiovascular disease (CVD) remains the most common cause of death worldwide and is more prevalent in chronic inflammatory states such as psoriasis. Recently, pro-protein convertase subtilisin/kexin type 9 (PCSK9) has gained attention as a novel therapeutic target in CVD due to its LDL cholesterol lowering capabilities. Therefore, we sought to investigate the relationship between PCSK9 and psoriasis. In patients with psoriasis (n=88), circulating PCSK9 levels are elevated compared to those of healthy volunteers (HV) (n=52) (Psoriasis: 253 ng/mL vs HV: 189 ng/mL, p<0.001) and are positively associated with coronary artery calcium (CAC) scores, beyond traditional cardiovascular risk factors (β =0.38, p<0.004).

Similarly, in our mouse model of psoriasis, we observe a 1.7-fold increase (p<0.0001) in circulating PCSK9 compared to that of littermate controls. Moreover, there is a robust relationship between circulating PCSK9 levels and psoriasis skin severity (β =0.92, p<0.001). We also find that although hepatic PCSK9 protein levels are unchanged in the psoriatic mice, low-density lipoprotein receptor (LDLR), the direct target of PCSK9, is significantly decreased at the protein level. Furthermore, we determine that both PCSK9 mRNA and protein levels are elevated in the lesional skin of psoriatic mice compared to those of littermate controls, a finding we confirmed in our psoriatic human skins. Taken together, we postulate that psoriatic lesional skin, specifically the epidermis, is the source for elevated plasma PCSK9, thereby decreasing hepatic LDLR, and suggesting a potential link between psoriasis and cardiovascular disease.