AI Article Synopsis
- The study explores how inhibiting MMP activity could potentially help prevent heart enlargement by reducing collagen turnover and fibrosis.
- At various ages (3, 5, and 12 months), transgenic mice with increased beta1-adrenergic receptor activity showed significant increases in collagen expression and MMP activity compared to normal controls.
- The findings suggest that overactivation of the sympathetic nervous system may lead to serious heart muscle remodeling and fibrosis, primarily through the increased activity of gelatinolytic MMP-2.
Article Abstract
Background: Inhibition of proteolytic MMP activity could be a therapeutic approach to prevent ventricular dilatation by diminishing collagen matrix turnover and interstitial fibrosis. We investigated the time-course of MMP/TIMP activity during transition from hypertrophy to ventricular dilatation in transgenic mice with myocyte overexpression of the human beta1-adrenergic receptor (beta1TG). These beta1TG mice were studied at 3 (normal function), 5 (hypertrophy) and 12 (ventricular dilatation) months of age compared to age-matched controls (WT).
Methods: Picro Sirius red staining and real-time PCR were performed for total collagen and for collagen type I and III quantification, respectively. MMP-activity assays (zymography), immunoblotting and real-time PCR experiments were done for gelatinase- (MMP-2, -9), collagenase- (MMP-1, -13), membrane-type MMP- (MT1- MMP; MMP-14) and TIMP expression measurements. To investigate beta1-integrin activity, integrin-linked kinase (ILK) expression was measured by immunoblotting.
Results: Compared to WT with normal cardiac function, interstitial collagen type I and III mRNA and protein expression increased 3.6-fold in beta1TG at 5 months of age with moderate fibrosis and cardiomyocyte hypertrophy and 17-fold in beta1TG at 12 months of age with severe fibrosis and ventricular dilatation. Protein expression of the collagenases MMP-1 and -13 as well as the gelatinase proMMP-2 increased in the beta1TG group with cardiac hypertrophy. Maximal activity of the gelatinase MMP-2 (3.5-fold vs.WT) was measured in beta1TG at 12 months of age with severe fibrosis and ventricular dilatation, accompanied by coexpression of MT1- MMP (3.8-fold vs.WT) colocalized to the cell membranes.
Conclusion: These data provide evidence that sympathetic overactivation can trigger interstitial matrix remodeling and fibrosis by induction of MMP/TIMP activity. In particular gelatinolytic MMP-2 activity accompanies ventricular dilatation and the development of heart failure.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779411 | PMC |
| http://dx.doi.org/10.1007/s00395-006-0635-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Surgical management of traumatic tricuspid regurgitation: a case report.
Eur Heart J Case Rep
January 2025
Department of Cardiac Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
Background: Traumatic tricuspid valve regurgitation is a rare condition related to blunt chest trauma. In the early phase, the patients may remain asymptomatic. Progressive tricuspid regurgitation leads to the development of symptoms thereafter.
View Article and Find Full Text PDFParadoxical improvement in exercise tolerance and peak VO2 consumption after treatment with ivabradine and beta-blockers in a patient with mild dilated cardiomyopathy and inappropriate sinus tachycardia-a case report.
Eur Heart J Case Rep
January 2025
Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
Background: Left bundle branch block (LBBB) is a rare conduction disorder in athletes associated with ventricular dyssynchrony, which can lead to left ventricular systolic dysfunction and exercise intolerance. Inappropriate sinus tachycardia (IST) is characterized by an excessive heart rate (HR) that is not related to physiological needs, often resulting in reduced exercise capacity. Managing these conditions in athletes can be challenging, as standard treatments like beta-blockers and ivabradine, while effective in controlling HR, are described to be associated with a reduction in maximal exercise performance.
View Article and Find Full Text PDFAnomalous origin of the left coronary artery from pulmonary artery mimicking antero-lateral ST-elevation myocardial infarction: a case report.
Eur Heart J Case Rep
January 2025
Cardiology Department, Meir Medical Center, Tchernichovsky St 59, Kfar Saba 4418001, Israel.
Background: Anomalous origin of the left coronary artery (LCA) from the pulmonary artery (PA) (ALCAPA) is a rare congenital abnormality. We present a case of an ALCAPA in a 25-year-old man.
Case Summary: A 25-year-old male with no past medical history was admitted to our intensive cardiac care unit after sudden cardiac arrest due to ventricular fibrillation and suspected acute coronary syndrome.
Germline deletion of Rgs2 and/or Rgs5 in male mice does not exacerbate left ventricular remodeling induced by subchronic isoproterenol infusion.
Physiol Rep
January 2025
Department of Physiology & Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Sympathoexcitation is a hallmark of heart failure, with sustained β-adrenergic receptor (βAR)-G protein signaling activation. βAR signaling is modulated by regulator of G protein signaling (RGS) proteins. Previously, we reported that Gα regulation by RGS2 or RGS5 is key to ventricular rhythm regulation, while the dual loss of both RGS proteins results in left ventricular (LV) dilatation and dysfunction.
View Article and Find Full Text PDFRelationship between myocardial fibrosis and left bundle branch block. Does it exist?
Cardiovasc Pathol
December 2024
Chazov National Medical Research Center of Cardiology, 121552, Academician Chazov str., 15a, Moscow, Russian Federation.
Aim: to assess the relation of focal and diffuse left ventricular (LV) fibrosis to left bundle branch block (LBBB).
Materials And Methods: 60 patients with dilated cardiomyopathy and LBBB (DCM-LBBB), 50 DCM-nonLBBB patients, 15 patients with LBBB and structurally normal heart (idiopathic LBBB) and 10 healthy volunteers (HV) underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). LGE LV images were post-proceed for core scar (CS) and gray zone (GZ) calculation.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!