Association of coronary microvascular dysfunction and cardiac bridge integrator 1, a cardiomyocyte dysfunction biomarker

Abstract

Background: Coronary microvascular dysfunction (CMD) is associated with heart failure with preserved ejection fraction (HFpEF); however, pathophysiology is not well described. Hypothesis:We hypothesized that CMD in women with suspected ischemia with no obstructive coronary artery disease (INOCA) is associated with cardiomyocyte dysfunction reflected by plasma levels of a cardiomyocyte calcium handling protein, cardiac bridge integrator 1 (cBIN1). Methods: Women with suspected INOCA undergoing coronary function testing were included. Coronary flow reserve, vasodilation to nitroglycerin, change in coronary blood flow (ΔCBF), and vasodilation to acetylcholine (ΔAch) were evaluated. cBIN1 score (CS) levels in these women (n = 39) were compared to women with HFpEF (n = 20), heart failure with reduced ejection fraction (HFrEF) (n = 36), and reference controls (RC) (n = 50). Higher CS indicates cardiomyocyte tubule dysfunction.Results: INOCA, HFpEF, and HFrEF women were older than RC (p < .05). Higher CS was associated with vasoconstriction to acetylcholine (r = À0.43, p = .011) with a trend towards lower ΔCBF (r = 0.30, p = .086). Higher CS was specific for ΔAch and ΔCBF but had limited sensitivity. INOCA women had higher CS than RC, but lower CS than HFpEF/HFrEF groups (p < .001).Conclusions: CS, a plasma biomarker indicating poor cardiomyocyte health, was higher in women with suspected INOCA as compared to RC, but lower than in

Circulating Biomarkers in Coronary Microvascular Dysfunction

“…Single studies have reported higher levels of serotonin, 75 stearic acid, 76 ornithine, 76 cardiac bridge integrator 1, 77 galactin‐3, 14 galectin‐4, 34 angiopoietin‐2 and tyrosine kinase‐2 receptor, 78 lymphocyte DNA damage, 79 NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), 62 and red blood cell distribution width 62 in CMD compared with control subjects, and no difference in apolipoprotein‐C levels in CMD compared with controls. 31 In a study of 97 subjects with CMD, galectin‐4 levels correlated with myocardial blood flow reserve.…”

“… 31 In a study of 97 subjects with CMD, galectin‐4 levels correlated with myocardial blood flow reserve. 34 The studies measuring serotonin, 75 cardiac bridge integrator 1, 77 galectin‐4, 34 and apolipoprotein‐C 31 assessed CMD directly by invasive and noninvasive techniques. The Klotho gene encodes a transmembrane protein, and the extracellular part of it is cleaved and can be measured in the blood.…”

Causal relationship between Alzheimer’s disease and unstable angina: a bidirectional Mendelian randomization analysis

“…rs6733839 is located near the bridging integrator 1 (BIN1) gene, which in turn affects the accumulation of the two major pathological hallmarks of AD, namely β-amyloid and Tau ( 57 ). BIN1 has also been found to be a regulator of transverse tubule function and calcium signaling in cardiomyocytes, and is associated with abnormal cardiac contraction, increasing the likelihood of malignant arrhythmias before heart failure ( 58 ); plasma levels of cardiac bridging integrator 1 (cBIN1) also indicative of the effects of coronary microvascular dysfunction on cardiomyocytes ( 59 ). Thus, this may be a potential mechanism for the relationship between the two diseases.…”

Latest from the WISE: Contributions to the Understanding of Ischemia and Heart Failure among Women with No Obstructive Coronary Arteries

“…A novel plasma biomarker of cardiomyocyte calcium handling protein, cardiac bridge interrogator 1 (cBIN-1), was recently found to be elevated in women with INOCA, reflecting cardiomyocyte tubule dysfunction [ 87 ]. Furthermore, higher cBIN1 score was associated with coronary endothelial dysfunction in these women.…”