Circulating Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Cardiac Amyloidosis

Overview

Journal J Am Heart Assoc

Specialty Cardiology & Vascular Diseases

Date 2013 Mar 30

PMID 23537813

Citations 16

Authors

Komei Tanaka

Eric E Essick

Gheorghe Doros

Kahraman Tanriverdi

Lawreen H Connors

David C Seldin

Flora Sam

Affiliations

Soon will be listed here.

Abstract

Background: Cardiac amyloidosis due to amyloid fibril deposition in the heart results in cardiomyopathy (CMP) with heart failure (HF) and/or conduction disturbances. Immunoglobulin light chain-related CMP (AL-CMP) features rapidly progressive HF with an extremely poor prognosis compared with a CMP due to the deposition of mutant (ATTR) amyloidosis or wild-type (senile systemic amyloidosis, SSA) transthyretin (TTR) proteins. Amyloid fibril deposition disrupts the myocardial extracellular matrix (ECM) homeostasis, which is partly regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). We therefore tested the hypothesis that circulating levels of MMPs and TIMPs in patients with AL-CMP and TTR-related CMP (TTR-CMP) are dissimilar and indicative of cardiac amyloid disease type.

Methods And Results: Fifty AL-CMP patients were compared with 50 TTR-CMP patients (composed of 38 SSA and 12 ATTR patients). Clinical and laboratory evaluations including echocardiography were performed at the initial visit to our center and analyzed. Serum MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were determined by ELISA. Compared with TTR-CMP patients, AL-CMP patients had higher levels of brain natriuretic peptide (BNP), troponin I (TnI), MMP-2, TIMP-1, and MMP-2/TIMP-2 ratio, despite less left ventricular (LV) hypertrophy and better preserved LV ejection fraction. Mortality was worse in AL-CMP patients than in TTR-CMP patients (log-rank P<0.01). MMP-2/TIMP-2 plus BNP and TnI showed the highest discriminative ability for distinguishing AL-CMP from TTR-CMP. Female sex (HR, 2.343; P=0.049) and BNP (HR, 1.041; P<0.01) were predictors for mortality for all patients with cardiac amyloidoses. Only BNP was a predictor of death in AL-CMP patients (HR, 1.090; P<0.01). There were no prognostic factors for all-cause death in TTR-CMP patients.

Conclusions: Circulating concentrations of MMPs and TIMPs may be useful in differentiating patients with AL-CMP from those with TTR-CMP, resulting in earlier diagnostic vigilance, and may add prognostic information. In addition to an elevated BNP level, female sex increased the risk of death in patients with cardiac amyloidoses.

Citing Articles

Mechanisms of damage and therapies for cardiac amyloidosis: a role for inflammation?.

Bellofatto I, Nikolaou P, Andreadou I, Canepa M, Carbone F, Ghigo A Clin Res Cardiol. 2024; .

PMID: 39167195 DOI: 10.1007/s00392-024-02522-2.

Cardiac Troponin in Patients With Light Chain and Transthyretin Cardiac Amyloidosis: State-of-the-Art Review.

De Michieli L, Cipriani A, Iliceto S, Dispenzieri A, Jaffe A JACC CardioOncol. 2024; 6(1):1-15.

PMID: 38510286 PMC: 10950441. DOI: 10.1016/j.jaccao.2023.12.006.

The Protein Network in Subcutaneous Fat Biopsies from Patients with AL Amyloidosis: More Than Diagnosis?.

Silvestre D, Brambilla F, Lavatelli F, Chirivi M, Canetti D, Bearzi C Cells. 2023; 12(5).

PMID: 36899835 PMC: 10000381. DOI: 10.3390/cells12050699.

Understanding AL amyloidosis with a little help from models.

Martinez-Rivas G, Bender S, Sirac C Front Immunol. 2022; 13:1008449.

PMID: 36458006 PMC: 9707859. DOI: 10.3389/fimmu.2022.1008449.

Molecular Mechanism of Pathogenesis and Treatment Strategies for AL Amyloidosis.

Ikura H, Endo J, Kitakata H, Moriyama H, Sano M, Fukuda K Int J Mol Sci. 2022; 23(11).

PMID: 35683015 PMC: 9181426. DOI: 10.3390/ijms23116336.

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