A study found that proprotein convertase subtilisin/kexin type 9 (PCSK9) levels correlate with the severity of pulmonary arterial hypertension (PAH). The study was conducted by researchers from the Shanghai Institute of Cardiovascular Diseases in China, who suggest that PCSK9 may be a potential therapeutic target for the disease.
“Receiver operating characteristic curve analysis showed the optimal cutoff value of serum PCSK9 concentration for predicting [idiopathic] PAH was 90.67 ng/mL, with a sensitivity of 90.0% and a specificity of 85.0%,” the researchers concluded.
They found that patients with idiopathic PAH (n=40) had increased levels of serum PCSK9 compared to control individuals (n=20). Moreover, PCSK9 levels were higher in patients classified into the World Health Organization functional classification (WHO-FC) group III or IV than in those in group I or II.
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PCSK9 levels in patients with idiopathic PAH were positively correlated with pulmonary arterial systolic pressure (r=0.653, P <.001), pulmonary arterial diastolic pressure (r=0.466, P =.002), mean pulmonary arterial pressure (mPAP; r=0.730, P <.001), pulmonary vascular resistance (r=0.488, P =.001), and right ventricle diameter (r=0.563, P <.001).
Multiple regression analysis showed that mPAP was strongly associated with serum PCSK9 levels (β=0.694, P <.001), independent of other variables.
Positive correlations were also found between PCSK9 levels in patients with idiopathic PAH and the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1), and N-terminal-prohormone B-type natriuretic peptide (NT-proBNP). Additionally, the levels of TNF-α, IL-6, MCP-1, and IL-1β were increased in patients with idiopathic PAH compared to control individuals.
PCSK9 has been implicated in a variety of processes, including cholesterol metabolism, adipogenesis, neurogenesis, platelet activation, inflammation, thrombosis, and myocardial infarct expansion. Increasing evidence suggests its involvement in the pathogenesis of inflammatory diseases, such as atherosclerosis, sepsis, psoriasis, rheumatoid arthritis, periodontitis, and Graves’ ophthalmopathy.
Zhong DX, Zhang Y, Jin Q, et al. Increased serum PCSK9 in patients with idiopathic pulmonary arterial hypertension: insights from inflammatory cytokines. Pulm Circ. 2021;11(4):20458940211051292. doi:10.1177/20458940211051292