Increased serum PCSK9 in patients with idiopathic pulmonary arterial hypertension: insights from inflammatory cytokines

Dong-Xiang Zhong; Yuan Zhang; Qi Jin; Xiao-Chun Zhang; Feng Zhang; Dan-Dan Chen; Li-Hua Guan; Da-Xin Zhou; Jun-Bo Ge

doi:10.1177/20458940211051292

Increased serum PCSK9 in patients with idiopathic pulmonary arterial hypertension: insights from inflammatory cytokines

Pulm Circ. 2021 Oct 12;11(4):20458940211051292. doi: 10.1177/20458940211051292. eCollection 2021 Oct-Dec.

Authors

Dong-Xiang Zhong¹, Yuan Zhang¹, Qi Jin¹, Xiao-Chun Zhang¹, Feng Zhang¹, Dan-Dan Chen¹, Li-Hua Guan¹, Da-Xin Zhou¹, Jun-Bo Ge¹

Affiliation

¹ Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important and major player in the pathophysiology of hypercholesterolemia and atherosclerosis. Recently, PCSK9 has been implicated in the pathogenesis of inflammatory diseases. Whether PCSK9 is involved in idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to investigate the relationship between PCSK9 and IPAH. Serum PCSK9, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β), and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme linked immunosorbent assay. Transthoracic echocardiography was performed among 40 IPAH patients and 20 control subjects. Hemodynamic data were collected via right heart catheterization in patients with IPAH. Serum PCSK9, TNF-α, IL-6, IL-1β, and MCP-1 levels were significantly higher in IPAH patients than in control subjects (p < 0.001). Among enrolled IPAH patients, PCSK9 levels were higher in WHO-FC III/IV patients compared with those in WHO-FC I/II (p < 0.05), and were positively correlated with TNF-α, IL-6, MCP-1, N-Terminal pro-brain natriuretic peptide, pulmonary arterial systolic pressure (r = 0.653, p < 0.001), pulmonary arterial diastolic pressure (r = 0.466, p = 0.002), mean pulmonary arterial pressure (mPAP, r = 0.730, <0.001), pulmonary vascular resistance (r = 0.488, p = 0.001), and right ventricle diameter (r = 0.563, p < 0.001). In multiple regression analysis, mPAP was strongly associated with serum PCSK9 (β = 0.694, p < 0.001), independent of other variables. Receiver operating characteristic curve analysis showed the optimal cutoff value of serum PCSK9 concentration for predicting IPAH was 90.67 ng/ml, with a sensitivity of 90.0% and a specificity of 85.0%. In conclusion, IPAH patients had elevated serum PCSK9 levels which correlated the presence and severity of pulmonary hypertension. PCSK9 may be a novel potential therapeutic target.

Keywords: NT-proBNP; inflammation; mean pulmonary arterial pressure; proprotein convertase subtilisin/kexin type 9.