FSTL-1 as a Novel Cardiokine of Cardiac Angiogenesis: A Systematic Review

Putri Karisa,1 Nova Sylviana,2– 4 Nita Fitria,4,5 Setiawan Setiawan2– 4 1Biomedical Science Master Program, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 2Department of Biomedical Science, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 3Physiology Molecular Laboratory, Biology Activity Division, Central Laboratory, Universitas Padjadjaran, Sumedang, West Java, Indonesia; 4Centre for Sport Science, Wellness, and Longevity, The Graduate School of Universitas Padjadjaran, Bandung, West Java, Indonesia; 5Biomedical Division, Department of Fundamental Nursing, Faculty of Nursing, Universitas Padjadjaran, Bandung, West Java, IndonesiaCorrespondence: Putri Karisa, Email [email protected]: Follistatin-like 1 (FSTL1) is recently becoming a novel cardiokine essential in cardiac angiogenesis. This cardiokine has shown a potential to promote angiogenesis and improve cardiac function, particularly in myocardial injury and ischemia. Despite the increasing relevance, there is no information on the mechanisms of FSTL1 in cardiac angiogenesis.Objective: This systematic review aimed to consolidate recent results on the role of FSTL1 in molecular pathways of cardiac angiogenesis.Methods: A comprehensive search was conducted using various databases, including PubMed, Scopus, SpringerLink, and ScienceDirect. Inclusion criteria were primary studies that investigated the role of FSTL1 in promoting cardiac angiogenesis with in vivo models. The risk of bias was assessed using SYRCLE risk of bias tool, and data were synthesized to evaluate the impact of FSTL1 on cardiac angiogenesis.Results: A total of 5 animal studies were included during the analysis. The results showed the role of FSTL1 as a novel cardiokine in inducing cardiac angiogenesis as assessed by protein examination and histologic analysis. In pathological conditions, the effects of ischemia on the heart increased the expression of FSTL1 as a form of protection for the heart through angiogenesis and as a marker of the disease severity. Furthermore, the molecular mechanisms of FSTL-induced angiogenesis had different signaling pathways, including activation of AMPK, TGFβ-Smad2/3, Akt/mTOR, Erk1/2, and DIP2A-PI3K. Studies showed increased capillary density and improved blood flow in cardiac tissues where FSTL1 was upregulated, suggesting a possible important role in improving cardiac function.Conclusion: FSTL1 showed a promising avenue for therapeutic development. Moreover, future studies should explore its role in cardiac angiogenesis in healthy populations.Keywords: angiogenesis, cardiovascular, FSTL1 protein, follistatin-related proteins, gene expression