Proteomics reveals high levels of vitamin D binding protein in myocardial infarction

Abstract

The pathogenic mechanisms underlying cardiovascular diseases involve significant alterations in myocardial gene and protein expression. Proteomics analysis can define new protein and peptide changes associated with cardiac pathology, including myocardial infarction. The aim of the present study was to analyze serum proteome of patients with ST-Elevation myocardial infarction (STEMI). Serum samples were collected from STEMI patients (age 65.0+/-10.3) at 5.3+/-2.7 hours after the onset of typical chest pain and before initiating standard therapy. Ten age- and sex-matched donors were used as controls. The samples were albumin- and IgG-depleted. Isotope-coded affinity tag method was employed to label cysteine residues and liquid chromatography-Tandem Mass Spectrometry analysis was performed to measure the labeled proteins. Our proteomic approach identified increased levels of vitamin D-binding protein precursor (VDB) in the serum of STEMI patients when compared to control donors. Western blot analysis confirmed the increase in VDB protein in STEMI patients. Moreover, fresh thrombotic plaques, obtained during primary angioplasty, showed high expression of VDB protein. Mechanistically, VDB protein reduces platelet aggregation and prolongs coagulation time ex vivo.

The Causal Effect of Vitamin D Binding Protein (DBP) Levels on Calcemic and Cardiometabolic Diseases: A Mendelian Randomization Study

“…For example, it may modulate bone development, innate immunity, and inflammatory responses [30] – [32] . DBP has also been purportedly linked with autoimmune and inflammatory diseases, aspirin resistance (i.e., failure of aspirin to inhibit platelet function) [33] , various arthritides [34] , and cardiometabolic outcomes [35] – [37] . Polymorphisms in the GC gene [38] have been associated with oral glucose tolerance, fasting insulin levels [39] , fracture risk [40] , and breast cancer [41] .…”

Vitamin D-Binding Protein Levels in Plasma and Gingival Crevicular Fluid of Patients with Generalized Aggressive Periodontitis

“…For example, DBP was found in the airways of patients with chronic obstructive pulmonary disease and acute respiratory distress syndrome and is believed to stimulate the monocyte inflammatory response in the lung by enhancing monocyte responses to C5-derived peptides [13]. In terms of cardiovascular disease, high expression of DBP protein has been found in fresh thrombotic plaques and in the serum of patients with ST elevation myocardial infarction [14]. Other disease states associated with altered DBP levels include tuberculosis, type 1 diabetes, sepsis, and cystic fibrosis [15–18].…”

Biomarker Discovery in Serum from Patients with Carotid Atherosclerosis

“…Actin filaments released from damaged cells have the potential to damage the vasculature and enhance thrombosis [33]. Recently, VTDB has been found in both the serum and thrombotic plaques of patients with acute myocardial infarction [34]. VTDB administration in vitro decreased platelet aggregation and prolonged coagulation [34].…”

“…Recently, VTDB has been found in both the serum and thrombotic plaques of patients with acute myocardial infarction [34]. VTDB administration in vitro decreased platelet aggregation and prolonged coagulation [34]. Further, patients with acute coronary syndromes have persistent elevation of plasma VTDB over 6 months compared to healthy volunteers [35].…”