Factors Associated with RANTES, EMMPIRIN, MMP2 and MMP9, and the Association of These Biomarkers with Cardiovascular Disease in a Multi-Ethnic Population

Abstract

Background: The growing cardiovascular disease (CVD) epidemic calls for further research to identify novel biomarkers for earlier detection and as potential therapeutic targets. Biomarkers Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMP-2, and MMP-9) are linked to proatherogenic and proinflammatory pathways of CVD development, the majority of which are coronary artery disease (CAD) and stroke. We evaluated potential factors affecting these four biomarkers and established their association with CVD. Methods: This is a cross-sectional analysis using a nested case-control design involving 580 participants aged 21–75 years from the prospective multi-ethnic cohort study. A total of 290 CVD cases and 290 age-and sex-matched controls were identified. All participants underwent interviews, health screenings, and provided blood samples, including biomarkers RANTES, EMMPRIN, and MMPs. CVD was defined based on previous medical history. Results: The average age of the participants was 55.7(SD = 10.3) years of age, and 34.6% were female. Arrhythmia history and low-density lipoprotein (LDL) levels were significant factors of logEMMPRIN (β = −0.124 [−0.245, −0.003] and β = 0.111 [0.0, 0.191], respectively). Only female sex (β = 0.189 [0.078, 0.300]) for logRANTES and age (β = 0.033 [0.010, 0.055]) for logMMP-2 and logMMP-9 were significant. The Indian ethnicity (β = 0.192 [0.048, 0.335]) and highly sensitive C-reactive protein (hs-CRP) levels (β = 0.063 [0.011, 0.116]) were statistically significant for logMMP-9. No association was detected between biomarkers and CVD. Conclusions: In this multi-ethnic study cohort, RANTES was associated with sex, EMMPRIN was associated with a history of arrhythmia and LDL levels, MMP-2 with age, and MMP-9 with ethnicity and hs-CRP levels. The biomarker serum levels were not associated with CVD.

The Diagnostic Model of Ligusticum Chuanxiong Hort. Against Cerebral Stroke Using Network Pharmacology and Transcriptomics Analyses

“…Previous studies have also demonstrated the association between these genes and cerebral stroke. For example, MMP9, TLR2, and TIMP1 are related to proinflammatory pathways following stroke [35][36][37] and inducing PTEN degradation can attenuate cerebral stroke [38]. Our data also revealed that age and sex can affect the diagnosis of stroke.…”

Identification and validation of genes associated with aging‐related cardiovascular disease

“…MMP9 (Matrix Metalloproteinase 9) levels are believed to increase inflammation and vascular wall degradation, resulting in increased arterial rigidity and a potential increased risk of hypertension and other cardiovascular diseases. However, in a recent clinical study involving 290 patients with CVD and 290 normal subjects, serum MMP9 levels were associated with ethnicity and C‐protein hypersensitivity, but not with coronary artery disease 52 . The study conducted by Lago J et al.…”

“…However, in a recent clinical study involving 290 patients with CVD and 290 normal subjects, serum MMP9 levels were associated with ethnicity and C-protein hypersensitivity, but not with coronary artery disease. 52 The study conducted by Lago J et al revealed that the upregulation of MMP9 in response to UVB stimulation contributes to skin aging, thereby indicating a significant association between MMP9 and the aging process. 53 The association between MMP9 and age was further validated through our analysis stratified by age.…”