# Myocardial Matrix Metalloproteinase 3 Protein Expression in Ischemic Heart Failure

**Authors:** Vitalija Siratavičiūtė, Dalia Pangonytė, Vaiva Lesauskaitė, Lina Utkienė, Lina Jusienė, Jolanta Marcinkevičienė, Milda Kuprytė, Dovydas Gečys, Vaiva Patamsytė, Zita Stanionienė, Reda Radikė

PMC · DOI: 10.3390/ijms27041697 · International Journal of Molecular Sciences · 2026-02-10

## TL;DR

This study shows that MMP3 protein levels increase in heart muscle cells as ischemic heart failure progresses, linking it to heart remodeling.

## Contribution

The study provides new evidence on the progression of MMP3 protein expression in human myocardium during ischemic heart failure.

## Key findings

- MMP3 protein expression increases significantly in early stages of ischemic heart failure.
- The highest MMP3 levels are observed in advanced stages of heart failure.
- MMP3 expression is associated with increased left ventricular mass and specific genetic variants.

## Abstract

Matrix metalloproteinase 3 (MMP3), in conjunction with other MMPs, plays a key role in myocardial remodeling by breaking down the extracellular matrix of the heart and the development of heart failure (HF). However, the existing data on MMP3 protein expression in human myocardium remains insufficient. The objective of the present study was to determine the expression of MMP3 protein in left ventricular myocardial cells at varying stages of ischemic HF. To this end, a quantitative and semi-quantitative immunohistochemical analysis was performed on 113 samples of left ventricular myocardium. A non-selective digital myocardial image analysis revealed that the stage A HF group exhibited higher MMP3 protein expression compared to the control group (p < 0.001). Subsequent increases in immunostaining intensity of MMP3 were observed in the stage B HF group (p < 0.001). In the stage C/D HF group, MMP3 expression reached its highest level (p < 0.001). The intensity of immunostaining exhibited comparable tendencies in both cardiomyocytes and non-cardiomyocytes. Increased levels of MMP3 immunostaining in both types of cells were associated with increased left ventricular mass. Subjects who carried the 5A allele and patients with the 5A homozygous genotype exhibited a higher propensity for increased immunostaining levels in both cardiomyocytes and non-cardiomyocytes when compared to those with the 6A/6A and 5A/6A genotype. These changes in MMP3 protein expression were associated with left ventricular myocardial remodeling in the progression of ischemic HF.

## Linked entities

- **Genes:** MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314]
- **Proteins:** MMP3 (matrix metallopeptidase 3)
- **Diseases:** heart failure (MONDO:0005252)

## Full-text entities

- **Genes:** VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, SERPINB2 (serpin family B member 2) [NCBI Gene 5055] {aka HsT1201, PAI, PAI-2, PAI2, PLANH2}, A2M (alpha-2-macroglobulin) [NCBI Gene 2] {aka A2MD, CPAMD5, FWP007, S863-7}, VTN (vitronectin) [NCBI Gene 7448] {aka V75, VN, VNT}, EPHB2 (EPH receptor B2) [NCBI Gene 2048] {aka BDPLT22, CAPB, DRT, EK5, EPHT3, ERK}, TNC (tenascin C) [NCBI Gene 3371] {aka 150-225, DFNA56, GMEM, GP, HXB, JI}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, SERPINA3 (serpin family A member 3) [NCBI Gene 12] {aka AACT, ACT, GIG24, GIG25}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, NID1 (nidogen 1) [NCBI Gene 4811] {aka NID}, SELL (selectin L) [NCBI Gene 6402] {aka CD62L, LAM1, LECAM1, LEU8, LNHR, LSEL}, SERPINC1 (serpin family C member 1) [NCBI Gene 462] {aka AT3, AT3D, ATIII, ATIII-R2, ATIII-T1, ATIII-T2}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}
- **Diseases:** ventricular mass (MESH:C536030), ventricular wall motion abnormalities (MESH:D006341), cardiomyopathies (MESH:D009202), sudden cardiac death (MESH:D016757), Non-communicable Diseases (MESH:D000073296), respiratory (MESH:D012131), Left ventricular dysfunction (MESH:D018487), valvular abnormalities (MESH:D006349), ischemic (MESH:D002545), diabetes mellitus (MESH:D003920), myocardial remodeling (MESH:D064752), injuries (MESH:D014947), fibrosis (MESH:D005355), systolic HF (MESH:D054143), cardiac remodeling (MESH:D020257), infarction (MESH:D007238), HF (MESH:D006333), idiopathic dilated cardiomyopathy (MESH:D002311), acute myocardial infarction (MESH:D009203), ischemic heart disease (MESH:D017202), death (MESH:D003643), C/ (OMIM:211750), arterial hypertension (MESH:D000081029)
- **Chemicals:** ethanol (MESH:D000431), xylene (MESH:D014992), EDTA (MESH:D004492), paraffin (MESH:D010232), doxycycline (MESH:D004318), Formalin (MESH:D005557), 3,3'-diaminobenzidine (MESH:D015100), DAB (MESH:C000469), Alcohol (MESH:D000438), hematoxylin (MESH:D006416), GV92511-2 (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs35068180, promoter -1171 5A, rs3025058

## Full text

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## Figures

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## References

65 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940760/full.md

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Source: https://tomesphere.com/paper/PMC12940760