Latent‑transforming growth factor β‑binding protein 2 accelerates cardiac fibroblast apoptosis by regulating the expression and activity of caspase‑3

Abstract

Cardiac fibrosis is a core process in the development of heart failure. However, the underlying mechanism of cardiac fibrosis remains unclear. Recently, a study found that in an isoproterenol (ISO)-induced cardiac fibrosis animal model, there is high expression of latent-transforming growth factor β-binding protein 2 (LTBP2) in cardiac fibroblasts. Whether LTBP2 serves a role in cardiac fibrosis is currently unknown. In the present study, mouse cardiac fibroblasts (MCFs) were treated with 100 µM/l ISO for 24, 48, or 72 h, and small interfering RNAs (siRNAs) were used to knockdown LTBP2. Reverse transcription-quantitative PCR and western blotting were used to determine gene and protein expression levels, respectively. Caspase-3 serves a key role in cell apoptosis and is related to cardiac fibrosis-induced heart failure. Caspase-3 activity was therefore determined using a caspase-3 assay kit, CCK8 was used to determine the rate of cell proliferation and apoptosis rates were quantified using a cell death detection ELISA kit. The present study demonstrated that cell apoptosis and LTBP2 expression increased in MCFs treated with 100 µM/l ISO in a time-dependent manner. Expression and activity of caspase-3 also increased in MCFs treated with 100 µM/l ISO for 48 h compared with the control group. In addition, ISO stimulation-induced MCF apoptosis, along with the increased expression of caspase-3 were partly abolished when LTBP2 was knocked down. In conclusion, LTBP2 expression increased in ISO-treated MCFs and accelerated mouse cardiac fibroblast apoptosis by enhancing the expression and activity of caspase-3. LTBP2 may therefore be a potential therapeutic target for treating patients with cardiac fibrosis.

Combining Deep Phenotyping of Serum Proteomics and Clinical Data via Machine Learning for COVID-19 Biomarker Discovery

“…Concerning the cardiometabolic biomarker panel, while LTBP2 was higher in patients with a “severe” outcome, KIT showed the opposite behavior. LTBP2 expression increases in response to myocardial stressors (e.g., pressure overload [ 96 ] or isoproterenol [ 97 ]) and has been associated with both cardiac [ 96 ] and pulmonary fibrosis [ 39 ]. Consistently, in patients with COVID-19, LTBP2 levels are related to pulmonary fibrosis [ 39 ] and are associated with disease severity [ 98 ].…”

Latent transforming growth factor beta binding protein 4: A regulator of mitochondrial function in acute kidney injury

“…Another remaining question is does LTBP4 protect against tissue damage in other regions? A key factor of the aging heart is cardiac fibrosis (Biernacka & Frangogiannis, 2011 ), which is modulated by TGF‐β activation and previously has been linked to LTBP2 activity (Shi et al., 2021 ). It remains unclear if, like LTBP2 (Shi et al., 2021 ), increased LTBP4 levels can “accelerate” cardiac fibroblast apoptosis, thus potentially slowing aging.…”

“…A key factor of the aging heart is cardiac fibrosis (Biernacka & Frangogiannis, 2011 ), which is modulated by TGF‐β activation and previously has been linked to LTBP2 activity (Shi et al., 2021 ). It remains unclear if, like LTBP2 (Shi et al., 2021 ), increased LTBP4 levels can “accelerate” cardiac fibroblast apoptosis, thus potentially slowing aging. Indeed, given that LTBP4 may impair progression to CKD (Su et al., 2023 ), this may already serve to slow renal aging.…”