Abstract
Background: Bone morphogenetic proteins-2 and -4 (BMPs) have been implicated in left ventricular remodeling (LVR) processes such as an inflammation and fibrogenesis. We hypothesized that this knowledge could be translated into clinics. Methods: We studied the dynamics of serum levels of BMPs, its correlation with markers of LVR and with parameters of echocardiography in patients (n = 31) during the six-month follow-up period after myocardial infarction (MI). Results: Elevated serum levels of BMPs decreased by the six-month follow-up period. BMP-2 decreased from the first day after MI, and BMP-4 decreased from the Day 14. The elevated level of BMP-2 at Day 1 was associated with a lower level of troponin I, reperfusion time and better left ventricular ejection fraction (LV EF) at the six-month follow-up. Elevated serum level of BMP-4 at Day 1 was associated with a lower level of a soluble isoform of suppression of tumorigenicity 2 (sST2), age and reperfusion time. An elevated level of BMP-2 at the six-month follow-up was associated with higher levels of BMP-4, high-sensitivity C-reactive protein (hCRP) and sST2. High serum level of BMP-2 correlated with high levels of hCRP and matrix metalloproteinase (MMP)-9 on Day 7. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day 7. The findings of multivariate analysis support the involvement of BMP-2 in the development of post-infarction LVR. Conclusions: Our research translates experimental data about the BMPs in the development of adverse LVR into the clinic. Elevated serum levels of BMPs decreased by the end of the six-month period after MI. BMP-2 decreased from the first day and BMP-4 decreased from Day 14. BMP-2 and BMP-4 were associated with the development of LVR. Their correlations with markers of inflammation, degradation of the extracellular matrix, hemodynamic stress and markers of myocardial damage further support our hypothesis. Diagnostic and predictive values of these BMPs at the development of post-infarction LVR in vivo should be investigated further.
Highlights
Acute myocardial infarction (AMI) with subsequent development of chronic heart failure (CHF)remains one of the leading causes of disability in the world [1]
Cells 2020, 9, 2179 that occurs under hemodynamic stress and is characterized by the formation of fibrotic scar tissue is a basis for the development of post-infarction adverse left ventricular remodeling (LVR) and CHF
We studied the early and late dynamics of serum levels of Bone morphogenetic proteins-2 and -4 (BMPs)-2 and BMP-4 and its correlation with levels of high sensitive C-reactive protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), matrix metalloproteinase-9 (MMP-9), a soluble isoform of suppression of tumorigenicity 2 and with parameters of echocardiography at Days 1, 3, 7 and 14 and at 6 months in patients with
Summary
Acute myocardial infarction (AMI) with subsequent development of chronic heart failure (CHF)remains one of the leading causes of disability in the world [1]. There are no clinical data about the serial assessment of the dynamics of serum levels of BMP-2 and BMP-4, their correlations with known markers of inflammation, degradation of the intercellular matrix and hemodynamic stress, with parameters of echocardiography in patients in the early and late post-infarction period. These results would provide us with an understanding of the role of BMPs in regeneration, inflammation and the development of postinfarction LVR in vivo. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day
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