Protective transcriptional mechanisms in cardiomyocytes and cardiac fibroblasts

Abstract

Heart failure is the leading cause of morbidity and mortality worldwide. Several lines of evidence suggest that physical activity and exercise can precondition the heart to improve the response to acute cardiac injury such as myocardial infarction or ischemia/reperfusion injury, preventing the progression to heart failure. It is becoming more apparent that cardioprotection is a concerted effort between multiple cell types and converging signaling pathways. However, the molecular mechanisms of cardioprotection are not completely understood. What is clear is that the mechanisms underlying this protection involve acute activation of transcriptional activators and their corresponding gene expression programs. Here, we review the known stress-dependent transcriptional programs that are activated in cardiomyocytes and cardiac fibroblasts to preserve function in the adult heart after injury. Focus is given to prominent transcriptional pathways such as mechanical stress or reactive oxygen species (ROS)-dependent activation of myocardin-related transcription factors (MRTFs) and transforming growth factor beta (TGFβ), and gene expression that positively regulates protective PI3K/Akt signaling. Together, these pathways modulate both beneficial and pathological responses to cardiac injury in a cell-specific manner.

Exercise Training Alleviates Cardiac Fibrosis through Increasing Fibroblast Growth Factor 21 and Regulating TGF-β1-Smad2/3-MMP2/9 Signaling in Mice with Myocardial Infarction

“…This result confirmed and suggested that both AET and RET could be included in the rehabilitation training of patients with MI, and patients can choose the suitable exercise mode according to their actual situation. Cardiac injury triggers the activation and differentiation of CFs and disrupts the balance between cardiomyocytes and CFs [40]. Activated CFs increased extracellular matrix (ECM) deposition [41].…”

“…To better study the mechanism of FGF21 on inhibiting cardiac fibrosis, CFs were isolated from the hearts of neonatal mice and treated with H 2 O 2 , rhFGF21 and AICAR. It is well known that oxidative stress is the essential factor of myocardial injury and cardiac fibrosis after MI [40]. In our study, H 2 O 2 treatment up-regulated the levels of TGF-β1, Smad2/3, MMP2, MMP9, and MDA, as well as COL-I and COL-III, and reduced SOD2 protein expression, suggesting the oxidative stress could activate TGF-β1-Smad2/3-MMPs signaling and increase the collagen secretion.…”

Single‐cell transcriptomics provides new insights into the role of fibroblasts during peritoneal fibrosis

“…18 Despite providing structural framework for tissues, the alterations in phenotype of fibroblasts may occur during different pathological conditions of different diseases. 2,19,20 Besides, even the same tissue can be populated with several fibroblast subsets with distinct features. 21 During PF, there are several sources of patho-logical fibroblasts, including mesothelial cells, resident fibroblasts, and even bone marrow-derived fibrocytes.…”

“…Although the mechanism involved in PF remains not fully clear, it has been known that accumulation of activated fibroblasts is one of the key steps in fibrotic progression 18 . Despite providing structural framework for tissues, the alterations in phenotype of fibroblasts may occur during different pathological conditions of different diseases 2,19,20 . Besides, even the same tissue can be populated with several fibroblast subsets with distinct features 21 .…”

Network Pharmacology-Based Investigation and Experimental Exploration of the Antiapoptotic Mechanism of Colchicine on Myocardial Ischemia Reperfusion Injury

“…Based on KEGG pathway enrichment and the result of molecular docking in the core targets, we chose the key proteins of PI3K/AKT/eNOS signaling pathway and the apoptosis-related protein Caspase-3 for validation the mechanisms underlying the anti-MIRI effects of colchicine. The PI3K/Akt signal pathway can regulate the migration, proliferation, differentiation, apoptosis and metabolism of various types of cells, which is connected to cardiomyocyte apoptosis ( Brand et al, 2019 ; Cui et al, 2020 ). PI3K is activated and generates phosphatidylinositol 3,4,5-trisphosphate, which induces the phosphorylation of AKT ( p -AKT), p -AKT then activates endothelial nitric oxide synthase (eNOS) and produces NO, NO produced by eNOS activation has been shown to play an important role in the process of MIRI ( Cohen et al, 2006 ; Ying et al, 2015 ).…”