The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding–Debanding of the Ascending Aorta

• Main Authors: Mireia Perera-Gonzalez, Attila Kiss, Philipp Kaiser, Michael Holzweber, Felix Nagel, Simon Watzinger, Eylem Acar, Petra Lujza Szabo, Inês Fonseca Gonçalves, Lukas Weber, Patrick Michael Pilz, Lubos Budinsky, Thomas Helbich, Bruno Karl Podesser
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: International Journal of Molecular Sciences
• Subjects: reverse remodeling; tenascin c; angiotensin-converting enzyme; cardiac magnetic resonance imaging
• Online Access: https://www.mdpi.com/1422-0067/22/4/2023
• ISSN: 1661-6596; 1422-0067

Background: Tenascin-C (TN-C) plays a maladaptive role in left ventricular (LV) hypertrophy following pressure overload. However, the role of TN-C in LV regression following mechanical unloading is unknown. Methods: LV hypertrophy was induced by transverse aortic constriction for 10 weeks followed by debanding for 2 weeks in wild type (Wt) and TN-C knockout (TN-C KO) mice. Cardiac function was assessed by serial magnetic resonance imaging. The expression of fibrotic markers and drivers (angiotensin-converting enzyme-1, ACE-1) was determined in LV tissue as well as human cardiac fibroblasts (HCFs) after TN-C treatment. Results: Chronic pressure overload resulted in a significant decline in cardiac function associated with LV dilation as well as upregulation of TN-C, collagen 1 (Col 1), and ACE-1 in Wt as compared to TN-C KO mice. Reverse remodeling in Wt mice partially improved cardiac function and fibrotic marker expression; however, TN-C protein expression remained unchanged. In HCF, TN-C strongly induced the upregulation of ACE 1 and Col 1. Conclusions: Pressure overload, when lasting long enough to induce HF, has less potential for reverse remodeling in mice. This may be due to significant upregulation of TN-C expression, which stimulates ACE 1, Col 1, and alpha-smooth muscle actin (α-SMA) upregulation in fibroblasts. Consequently, addressing TN-C in LV hypertrophy might open a new window for future therapeutics.