Clinical & Experimental Cardiology
Open Access

Abstract

Extracellular Matrix Remodeling and Inflammation in Transthyretin Amyloidosis

Alessia Argirò, Giulia Guidotti, Martina Berteotti*, Viola Liberati, Mattia Zampieri, Federico Perfetto, Marco Allinovi, Anna Poggesi, Carlo Di Mario, Rossella Marcucci and Francesco Cappelli

Introduction and objectives: Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is an interstitial disease characterized by extracellular deposition of amyloid fibrils. The purpose of the study was to assess if inflammation and Extracellular Matrix (ECM) markers are altered in ATTR, as already known for light chain amyloidosis.

Methods: Fourty-nine patients with ATTR-CM were enrolled in an observational, prospective, cross-sectional, single- center study and underwent clinical, instrumental and biohumoral markers evaluation. The laboratory results were compared to those of an age and sex-matched cohort of 50 patients with sole atrial fibrillation.

Results: Mean age was 78 ± 5 years and 83% of patients were men. Forty-two (86%) had acquired ATTR, 7 (14%) had hereditary ATTR. Patients with ATTR-CM presented higher concentration of inflammatory biomarkers, such as IL-6 (2.9 pg/ml (IQR 1.6-1.33) vs. 1.56 pg/ml (IQR 0.43-3.12), p=0.002), IL-8 (17.21 pg/ml (IQR 11.94-34.8) vs. 8.54 pg/ml (IQR 5.15-13.3), p<0.001) and VEGF (101.03 pg/ml (IQR 59.05-146.2) vs. 62.31 pg/ml (IQR 35.28- 112.43), p=0.011), while anti-inflammatory IL-10 was lower (0.2 pg/ml (IQR 0.1-0.2) vs. 2.89 pg/ml (IQR 0.33-3.46), p<0.001). Serum levels of metalloprotease MMP-12, TIMP-1 and TIMP-3 were significantly higher in ATTR-CM, with an increased ratio between MMP-12 and TIMP-2, -3 and -4 in ATTR-CM expressing an imbalance towards ECM degradation.

Conclusion: These data suggest that ATTR-CM is characterized by increased inflammation and an unbalance in ECM homeostasis, with degradation prevailing over synthesis of ECM.

Published Date: 2024-05-01; Received Date: 2024-04-01