CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 5, September/October 2022 228 AFRICA Cardiovascular Topics PRELP promotes myocardial fibrosis and ventricular remodelling after acute myocardial infarction by the wnt/β–catenin signalling pathway Yu Zhang, Chunli Fu, Shaohua Zhao, Honglei Jiang, Wei Li, Xiangju Liu Abstract Objectives: Proline/arginine-rich end leucine-rich repeat protein (PRELP) has been reported to contribute to the remodelling of cardiovascular tissues in the ischaemia–reperfusion injury model. However, research is lacking on the role of PRELP in myocardial fibrosis and ventricular remodelling, and the mechanism through which PRELP brings about these changes is not clear. This study aimed to evaluate the role of PRELP in ventricular remodelling and myocardial fibrosis following acute myocardial infarction (AMI) and to explore the underlying mechanism. Methods: In this study, we established AMI mouse and cellculture models in an oxygen–glucose deprivation environment. Results: We found that over-expression of PRELP increased the infarct size and interstitial fibrotic area. Expression of the wnt/β–catenin pathway molecules, which are downstream of PRELP, increased more in the PRELP over-expression group than in the AMI group. Conclusions: Our results showed that PRELP, through the wnt/β–catenin signalling pathway, led to myocardial fibrosis and ventricular remodelling following AMI. Keywords: PRELP, myocardial fibrosis, acute myocardial infarction, wnt, β-catenin Submitted 25/2/21; accepted 20/12/21 Published online 29/6/22 Cardiovasc J Afr 2022; 33: 228–233 www.cvja.co.za DOI: 10.5830/CVJA-2022-001 Acute myocardial infarction (AMI), a serious and common cardiovascular disorder, is the leading cause of heart failure and sudden death,1-3 with increasing incidence worldwide.4 Myocardial fibrosis is an important pathological characteristic linked to AMI.5,6 It can lead to elevated rigidity, induce myocardial sclerosis, trigger ventricular remodelling, affect ventricular compliance and eventually induce heart failure.7 Therefore, more effort should be made to identify the molecular mechanisms of myocardial fibrosis. This will help provide novel insights into therapeutic targets and uncover effective strategies to alleviate myocardial fibrosis and ventricular remodelling following AMI. The small leucine-rich repeat protein family (SLRR), located in the extracellular matrix of connective tissue, has been found to play an important role in myocardial fibrosis and ventricular remodelling.8,9 There are several members in the SLRRs, such as biglycan, decorin, lumican and glypican-6. Recent studies showed that inhibition of biglycan or lumican expression can reduce myocardial fibrosis.10,11 It was also shown that glypican-6 is involved in cardiac remodelling by the extracellular signalrelated kinase (ERK) signalling pathway.12 Proline/arginine-rich end leucine-rich repeat protein (PRELP), which is another member of the SLRRs, can bind to the basement membranes of connective tissues more easily compared to other members of the SLRRs, as it contains a positively charged N-terminus rich in proline and arginine residue.13 Javier et al., for the first time, reported that several members of the small leucinerich proteoglycan family, including asporin and PRELP, were shown to contribute to cardiac remodelling.14 However, there is little research about PRELP’s role in myocardial fibrosis and ventricular remodelling post AMI. The mechanism by which PRELP brings about these changes is also not clear. The wnt signalling pathway is a relatively silent pathway that regulates important cellular activity such as cell proliferation, differentiation and apoptosis. β-catenin has been found to be one of the most important members in the wnt signalling pathway. The other downstream members of this pathway are glycogen synthase kinase 3 beta (GSK3β), matrix metallopeptidase 9 (MMP9), c-myc and tissue inhibitor of metalloproteinases-1 (TIMP-1). Previous studies have shown that wnt signalling gets activated following AMI.15 Sufficient activation of this signalling pathway can decrease the infarct size of the heart and alleviate heart failure, while excess activation can increase myocardial fibrosis and infarct sizes.16,17 A recent research study suggested that PRELP can regulate the differentiation of osteoblasts by the Shandong Key Laboratory of Cardiovascular Proteomics, Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China Yu Zhang, MM, zhangy19851208@126.com Chunli Fu, MD Shaohua Zhao, MD Xiangju Liu, MD, xiangjuliu@163.com Department of Cardiology, Shandong Provincial Western Hospital, Jinan, Shandong, People’s Republic of China Honglei Jiang, MD Department of Anesthesia, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China Wei Li, MD
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