Procollagen type I carboxy-terminal propeptide (PICP) and MMP-2 are potential biomarkers of myocardial fibrosis in patients with hypertrophic cardiomyopathy

Cardiovasc Pathol. 2019 Nov-Dec:43:107150. doi: 10.1016/j.carpath.2019.107150. Epub 2019 Aug 28.

Abstract

Background: Whether current proposed biomarkers of myocardial fibrosis (BMFs) actually reflect the changes in fibrous characteristics of myocardial tissue remains unclear. The relation between peripheral BMFs and histological myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) has been unknown.

Methods and results: We studied 52 HCM patients who underwent a transaortic extended septal myectomy. Complete medical history was collected, and related examinations were performed. Echocardiography and cardiovascular magnetic resonance were employed to characterize cardiac morphology and function. Procollagen type I carboxy-terminal propeptide (PICP), C-terminal telopeptide of type I collagen (CITP), matrix metalloproteinases (total MMP-2 and total MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels in both plasma and myocardial tissues were determined and compared. Myocardial fibrosis was detected with Masson's trichrome staining, and collagen volume fraction (CVF) was calculated. There was a significant correlation between plasma PICP levels and myocardial PICP contents (r=0.382, P=.007). Besides, plasma PICP (r=0.332, P=.020) levels correlated positively with CVF. In addition, plasma TIMP-1 levels were significantly correlated with myocardial TIMP-1 contents (r=0.282, P=.043). Plasma MMP-2 levels correlated positively with CVF (r=0.379, P=.006). Patients who took calcium channel blockers (CCBs; diltiazem or verapamil) had significantly lower plasma PICP levels, myocardial PICP content, and CVF in comparison with those who did not take CCBs.

Conclusions: In patients with HCM, plasma PICP and MMP-2 levels quantitatively reflect myocardial fibrosis, suggesting that PICP and MMP-2 may be used as reliable BMFs. CCBs may attenuate cardiac fibrosis in patients with HCM.

Keywords: Hypertrophic cardiomyopathy; MMP-2; Myocardial fibrosis; Procollagen type I carboxy-terminal propeptide (PICP).

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / analysis
  • Biomarkers / blood
  • Cardiomyopathy, Hypertrophic / blood
  • Cardiomyopathy, Hypertrophic / metabolism*
  • Cardiomyopathy, Hypertrophic / pathology
  • Cardiomyopathy, Hypertrophic / surgery
  • Child
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibrosis
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / analysis*
  • Matrix Metalloproteinase 2 / blood
  • Middle Aged
  • Myocardium / chemistry*
  • Myocardium / pathology
  • Peptide Fragments / analysis*
  • Peptide Fragments / blood
  • Procollagen / analysis*
  • Procollagen / blood
  • Young Adult

Substances

  • Biomarkers
  • Peptide Fragments
  • Procollagen
  • procollagen type I carboxy terminal peptide
  • MMP2 protein, human
  • Matrix Metalloproteinase 2