TY - JOUR
T1 - Coronary endothelial dysfunction is associated with elevated serum PCSK9 levels in people with HIV independent of low-density lipoprotein cholesterol
AU - Leucker, Thorsten M.
AU - Weiss, Robert G.
AU - Schär, Michael
AU - Bonanno, Gabriele
AU - Mathews, Lena
AU - Jones, Steven R.
AU - Brown, Todd T.
AU - Moore, Richard
AU - Afework, Yohannes
AU - Gerstenblith, Gary
AU - Hays, Allison G.
N1 - Funding Information:
This work was supported by the National Institutes of Health (5T32HL007227-42 and HL125059), the American Heart Association (17GRNT33670943), the Johns Hopkins University Center for AIDS Research (P30AI094189 and 1704611701), the Johns Hopkins Magic That Matters Grant, the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, and the Clarence Doodeman Endowment of Johns Hopkins.
Publisher Copyright:
© 2018 The Authors.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Background—HIV+ people are at increased risk of coronary artery disease, but the responsible mechanisms are incompletely understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is traditionally recognized for its importance in cholesterol metabolism; however, recent data suggest an additional, low‐density lipoprotein receptor–independent adverse effect on endothelial cell inflammation and function. We tested the hypotheses that PCSK9 levels are increased and that abnormal coronary endothelial function is related to PCSK9 serum levels in HIV+ individuals. Methods and Results—Forty‐eight HIV+ participants receiving antiretroviral therapy with suppressed viral replication, without coronary artery disease, and 15 age‐ and low‐density lipoprotein cholesterol–matched healthy HIV− subjects underwent magnetic resonance imaging to measure coronary endothelial function, quantified as percentage change in coronary artery cross‐sectional area during isometric handgrip exercise, an endothelial‐dependent stressor; and blood was obtained for serum PCSK9 and systemic vascular biomarkers. Data are presented as mean±SD. Mean serum PCSK9 was 65% higher in the HIV+ subjects (302±146 ng/mL) than in the HIV− controls (183±52 ng/mL, P<0.0001). Coronary endothelial function was significantly reduced in the HIV+ versus HIV− subjects (percentage change in coronary artery cross‐sectional area, 2.9±9.6% versus 11.1±3.7%; P<0.0001) and inversely related to PCSK9 (R=−0.51, P<0.0001). Markers of endothelial activation and injury, P‐selectin and thrombomodulin, were also significantly increased in the HIV+ subjects; and P‐selectin was directly correlated with serum PCSK9 (R=0.31, P=0.0144). Conclusions—Serum PCSK9 levels are increased in treated HIV+ individuals and are associated with abnormal coronary endothelial function, an established measure of vascular health.
AB - Background—HIV+ people are at increased risk of coronary artery disease, but the responsible mechanisms are incompletely understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is traditionally recognized for its importance in cholesterol metabolism; however, recent data suggest an additional, low‐density lipoprotein receptor–independent adverse effect on endothelial cell inflammation and function. We tested the hypotheses that PCSK9 levels are increased and that abnormal coronary endothelial function is related to PCSK9 serum levels in HIV+ individuals. Methods and Results—Forty‐eight HIV+ participants receiving antiretroviral therapy with suppressed viral replication, without coronary artery disease, and 15 age‐ and low‐density lipoprotein cholesterol–matched healthy HIV− subjects underwent magnetic resonance imaging to measure coronary endothelial function, quantified as percentage change in coronary artery cross‐sectional area during isometric handgrip exercise, an endothelial‐dependent stressor; and blood was obtained for serum PCSK9 and systemic vascular biomarkers. Data are presented as mean±SD. Mean serum PCSK9 was 65% higher in the HIV+ subjects (302±146 ng/mL) than in the HIV− controls (183±52 ng/mL, P<0.0001). Coronary endothelial function was significantly reduced in the HIV+ versus HIV− subjects (percentage change in coronary artery cross‐sectional area, 2.9±9.6% versus 11.1±3.7%; P<0.0001) and inversely related to PCSK9 (R=−0.51, P<0.0001). Markers of endothelial activation and injury, P‐selectin and thrombomodulin, were also significantly increased in the HIV+ subjects; and P‐selectin was directly correlated with serum PCSK9 (R=0.31, P=0.0144). Conclusions—Serum PCSK9 levels are increased in treated HIV+ individuals and are associated with abnormal coronary endothelial function, an established measure of vascular health.
KW - Endothelial function
KW - HIV
KW - Inflammation
KW - Magnetic resonance
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U2 - 10.1161/JAHA.118.009996
DO - 10.1161/JAHA.118.009996
M3 - Article
C2 - 30371326
AN - SCOPUS:85055616196
SN - 2047-9980
VL - 7
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 19
M1 - e009996
ER -