Platelet surface expression of cyclophilin A is associated with increased mortality in patients with symptomatic coronary artery disease

Abstract

Background: Cyclophilin A (CyPA) is an important intracellular molecule mediating essential cellular functions such as signaling and protein folding. Enhanced CyPA platelet surface expression is associated with hypertension and hypercholesterolemia in patients with stable coronary artery disease (CAD). In patients with acute myocardial infarction CyPA platelet surface expression is significantly decreased. The aim of this study was to investigate possible associations of CyPA platelet surface expression and a clinically relevant CyPA single-nucleotide polymorphism (CyPA PPIA rs6850) with prognosis in patients with symptomatic cardiovascular disease.Materials and methods: Blood was obtained from 335 consecutive patients with symptomatic CAD. All patients were followed up for 1080 days for endpoints allcause death, myocardial infarction (MI), ischemic stroke, and bleeding. The primary combined endpoint was defined as a composite of all-cause death and/or MI and/or ischemic stroke. Cyclophilin A platelet surface expression levels less than or equal to the median were significantly associated with a worse prognosis (combined endpoint and all-cause death) when compared to CyPA greater than the median. Genotyping for CyPA PPIA rs6850 was performed in 752 patients with symptomatic CAD.Homozygous carriers of the minor allele showed a significantly worse cumulative event-free survival for both combined endpoint and MI when compared to carriers of the major allele. Conclusion:The CyPA platelet surface expression is associated with mortality whereas CyPA PPIA rs6850 is associated with recurrent MI in patients with | 235 RATH eT Al.

Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study

“…This is supported by a study among diabetes patients that demonstrated that rs6850 was associated with increased plasma levels of Cyclophillin A, and an increased likelihood of cardiovascular diseases among patients with or without diabetes [24]. Additionally, Rath et al also reported that rs6850 was associated with recurrent myocardial infarction among patients with symptomatic coronary artery disease [25]. Taken together, these findings could imply that rs6850 increases Cyclophillin A protein expression that affects signaling and protein folding thus promoting susceptibility to various disease pathologies including HIV infectivity and disease progression among non-controllers.…”

Variations In Trim5α And Cyclophilin A Genes Among HIV-1 Elite Controllers and Non Controllers In Uganda; A Laboratory-Based Cross-sectional Study

“…This is supported by a study among diabetes patients that demonstrated that rs6850 was associated with increased plasma levels of Cyclophillin A, and an increased likelihood of cardiovascular diseases among patients with or without diabetes (24). Additionally, Rath et al (2019) also reported that rs6850 was associated with recurrent myocardial infarction among patients with symptomatic coronary artery disease (25). Taken together, these ndings could imply that rs6850 increases Cyclophillin A protein expression that affects signaling and protein folding thus promoting susceptibility to various disease pathologies including HIV infectivity and disease progression among non-controllers.…”

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

“…CyPA is an intracellular protein that is expressed under inflammatory conditions by several cell types; some of them have been shown to secrete CyPA during in the early stages of pathologies that include atherosclerosis, coronary artery disease (CAD), and acute myocardial infarction [11]. During atherosclerosis, CyPA mediates ox-LDL-induced macrophage activation [12], and it was recently shown that inhibition of CyPA degradation is also prevented by ox-LDL via a mechanism which enlarges early atherosclerotic burden [13].…”