Coordinated suppression of lectin complement pathway effectors and upregulation of SERPING1 defines a thrombo-inflammatory regulatory signature in Acute Coronary disease.

BACKGROUND: Cardiovascular disease (CVD), the leading global cause of death, Acute coronary disease (ACS) is the highest mortality among CVD. Which is driven by thrombo-inflammatory processes involving oxidative stress, endothelial dysfunction, and innate immune dysregulation. The lectin complement pathway contributes to coagulation through thrombin-like activity and fibrin cross-linking, yet its transcriptional regulation under oxidative stress in human ACS remains unclear. We investigated whether acute coronary syndrome is associated with coordinated dysregulation of lectin pathway effector genes and the regulatory gene SERPING1.

METHODS: In this cross-sectional study, 100 patients with clinically confirmed ACS and 50 healthy controls were enrolled. Systemic oxidative stress was assessed using serum superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). The mRNA expression of MBL2, MASP1, MASP2, and SERPING1 was quantified in peripheral blood mononuclear cells (PBMCs) by RT-qPCR. ACS and control groups differed substantially in age, smoking, and alcohol use. The Mann-Whitney U test was used to compare continuous variables between the two independent groups, and multivariable linear regression was used to adjust for age, smoking, and alcohol use.

RESULTS: ACS patients showed significant oxidative imbalance, with reduced SOD (p < 0.0001), elevated MDA (p = 0.007), while CAT remained unchanged (p = 0.277) and significant downregulation of MBL2 (p = 0.017), MASP1 (p = 0.027), and MASP2 (p < 0.0001), alongside upregulation of SERPING1 (p = 0.001). After adjusting for age, smoking, and alcohol use, the association between ACS status and SERPING1 expression remained significant using both classical and heteroscedasticity-robust inference (adjusted p = 0.0007) and in an age-restricted sensitivity subsample (p = 0.003). The SOD reduction was attenuated to borderline significance after adjustment (robust p = 0.02), and the MBL2, MASP1, MASP2, and MDA associations did not reach significance after adjustment, indicating that these differences are substantially, though not necessarily entirely, explained by the between-group age and lifestyle imbalance.

CONCLUSIONS: ACS is associated with acute-phase systemic oxidative stress and altered lectin pathway gene expression, most notably a robust, adjustment-independent upregulation of SERPING1 that persists after accounting for age, smoking, and alcohol use. The downregulation of MBL2, MASP1, and MASP2 effector genes was attenuated after adjustment for these covariates and should be interpreted cautiously as a disease-associated signature until confirmed in age- and lifestyle-matched cohorts. These findings nonetheless identify SERPING1, and by extension the MASP-SERPING1 axis, as a candidate biomarker and therapeutic target meriting prospective, matched-cohort validation, with protein-level confirmation of the acute-phase transcriptional response captured here.