Low acylation stimulating protein levels are associated with cardiometabolic disorders-secondary to autoimmune activation?

Abstract

Objective: We investigated the possible association of serum acylation stimulating protein (ASP) with cardiometabolic disorders and the evidence of autoimmune activation.

Methods: Population-based randomly selected 1024 participants were cross-sectionally and prospectively analyzed. ASP concentrations were measured with a validated ELISA kit. Correlations were sought separately in subjects with no cardiometabolic disorders (n=427) designated as "healthy."

Results: ASP was positively correlated with total testosterone and inversely correlated with platelet activating factor (PAF), PAF-acetylhydrolase (AH), in each gender, and positively correlated in "healthy" men with lipoprotein [Lp](a) and apolipoprotein B. Correlations of ASP with PAF values ≥22 nmol/L were abolished, contrasted to a strongly inverse one in subjects with PAF <22 nmol/L. In linear regression analyses in the whole sample, ASP was inversely associated independently with PAF and PAF-AH and, in men, positively with Lp(a) and sex hormone-binding globulin. Prevalent and (at 2.0 years' follow-up) incident metabolic syndrome (MetS, n=393), diabetes (n=154), and coronary heart disease (CHD, n=171) were analyzed by sex-, age-, and Lp(a)-adjusted logistic regression, using tertiles of ASP and PAF. The lower two (<42 nmol/L) ASP tertiles were a risk factor in combined sexes for MetS and diabetes. In women, incident CHD was predicted by either reduced or elevated ASP tertiles.

Conclusion: Findings can be explained by the notion of operation of immune responses against both ASP and oxidized PAF-like lipids of Lp(a) to yield for "reduced" values and increased likelihood of cardiometabolic disorders.

Figure 1

The plot depicts the correlations between log-transformed acylation stimulating hormone (ASP) and dichotomized platelet activating factor (PAF) concentrations in (a) 177 men (left) and 165 women without cardiometabolic disorders and (b) 221 men (left) and 248 women with cardiometabolic disorders. Individuals with PAF <22 nmol/L (indicated in blue) demonstrate strongly inverse relationship to ASP (ranging from r=-0.52 to -0.64) regardless of gender or health status. This stands in sharp contrast to people with PAF >22 nmol/L (in green), in whom correlations are abolished (ranging from r=-0.18 to +0.05)