METHODS: Primary SFb isolated from knee synovium of OA obese (OA-ob:SFb), OA-pre-obese (OA-Pob:SFb), non-OA arthroscopic (scope:SFb), and non-OA arthroscopic with cartilage damage (scope-CD:SFb) were exposed to OA-conditioned media (OACM), derived from OA obese (OA-ob:CM), OA-pre-obese (OA-Pob:CM), and mechanical stretch at either 0 %, 6 % or 10 % for 24 h. Differences in the mRNA levels of genes involved in extracellular matrix production, inflammation and secretory activity were measured.
RESULTS: Despite the significant BMI differences between the OA-ob and OA-Pob groups, OA-Pob has more patients with underlying dyslipidaemia, and low-grade synovitis with higher levels of secreted proteins, CXCL8, COL4A1, CCL4, SPARC and FGF2 in OA-Pob:CM. All primary SFb exhibited anti-proliferative activity with both OA-CM. Mechanical stretch stimulated lubricin production in scope:SFb, higher TGFβ1 and COL1A1 expressions in scope-CD:SFb. OA-Pob:CM stimulated greater detrimental effects than the OA-ob:CM, with higher pro-inflammatory cytokines, IL1β, IL6, COX2 and proteases such as aggrecanases, ADAMTS4 and ADAMTS5, and lower ECM matrix, COL1A1 expressions in all SFb. OA-ob:SFb were unresponsive but expressed higher pro-inflammatory cytokines under OA-Pob:CM treatment.
CONCLUSION: Both mechanical and inflammatory stressors regulate SFb molecular functions with heterogeneity in responses that are dependent on their pathological tissue of origins. While mechanical stretch promotes a favorable effect with enhanced lubricin production in scope:SFb and TGFβ1 and COL1A1 in scope-CD:SFb, the presence of excessively high OA-associated inflammatory mediators in OA-Pob:CM, predominantly SPARC, CXCL8 and FGF2 drive all SFb regardless of pathology, towards greater pro-inflammatory activities.
OBJECTIVE: The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results.
METHODS: By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire.
RESULTS: Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models.
CONCLUSIONS: The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/31885.