Circulating osteogenic proteins are associated with coronary artery calcification and increase after myocardial infarction

Author(s)

Pesaro, Antonio E. ^[1] ; Katz, Marcelo ^[1] ; Liberman, Marcel ^[1] ; Pereira, Carolina ^[1] ; Mangueira, Cristovao L. P. ^[1] ; de Carvalho, Ana E. Z. ^[1] ; Carvalho, Karina S. ^[1] ; Nomura, Cesar H. ^[1] ; Franken, Marcelo ^[1] ; Serrano Jr, V, Carlos

Affiliation

^[1] V, Hosp Israelita Albert Einstein, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 13, n. 8 AUG 23 2018.
• Web of Science Citations: 1

Abstract

Background Coronary artery calcification (CAC) and atherosclerotic inflammation associate with increased risk of myocardial infarction (MI). Vascular calcification is regulated by osteogenic proteins (OPs). It is unknown whether an association exists between CAC and plasma OPs and if they are affected by atherothrombotic inflammation. We tested the association of osteogenic and inflammatory proteins with CAC and assessed these biomarkers after MI. Methods Circulating OPs (osteoprotegerin, RANKL, fetuin-A, Matrix Gla protein {[}MGP]) and inflammatory proteins (C-reactive protein, oxidized-LDL, tumoral necrosis factor-alpha, transforming growth factor {[}TGF]-beta 1) were compared between stable patients with CAC (CAC >= 100 AU, n = 100) and controls (CAC = 0 AU, n = 30). The association between biomarkers and CAC was tested by multivariate analysis. In patients with MI (n = 40), biomarkers were compared between acute phase and 1-2 months post-MI, using controls as a baseline. Results MGP and fetuin-A levels were higher within individuals with CAC. Higher levels of MGP and RANKL were associated with CAC (OR 3.12 {[}95% CI 1.20-8.11], p = 0.02; and OR 1.75 {[}95% CI 1.04-2.94] respectively, p = 0.035). After MI, C-reactive protein, OPG and oxidized-LDL levels increased in the acute phase, whereas MGP and TGF-beta 1 increased 1-2 months post-MI. Conclusions Higher MGP and RANKL levels associate with CAC. These findings highlight the potential role of these proteins as modulators and markers of CAC. In addition, the post-MI increase in OPG and MGP, as well as of inflammatory proteins suggest that the regulation of these OPs is affected by atherothrombotic inflammation. (AU)

• FAPESP's process: 13/06799-0 - Evaluation of the osteogenic regulating proteins and inflammatory profile of patients with acute myocardial infarction and asymptomatic subjects with coronary artery calcification
• Grantee: Antonio Eduardo Pereira Pesaro
• Support Opportunities: Regular Research Grants