hKLK alleviates myocardial fibrosis in mice with viral myocarditis (2024)

J Appl Biomed 21:15-22, 2023|DOI:10.32725/jab.2023.005

hKLK alleviates myocardial fibrosis in mice with viral myocarditis

Youfa Qin^{1, 2, 5, *}, Xiaomei Ye¹, Ye Luo^{1, 5}, Luting Peng^{1, 2}, Guanghui Zhou^{3, *}, Yongkun Zhu⁴, Chunyu Pan¹

¹Affiliated Dongguan Shilong People's Hospital of Southern Medical University, SSL Central Hospital of Dongguan City, Department of Clinical Pharmacy, Dongguan, Guangdong, China

²Southern Medical University, School of Pharmaceutical Sciences, Guangzhou, Guangdong, China

³Affiliated Dongguan Shilong People's Hospital of Southern Medical University, SSL Central Hospital of Dongguan City, Department of traditional Chinese medicine & Medical rehabilitation, Dongguan, Guangdong, China

⁴Affiliated Dongguan Shilong People's Hospital of Southern Medical University, SSL Central Hospital of Dongguan City, Department of Pharmacy, Dongguan, Guangdong, China

⁵Guangdong Medical University, School of Pharmacy, Dongguan, Guangdong, China

Myocardial fibrosis is the most serious complication of viral myocarditis (VMC). This study aimed to investigate the therapeutic benefits and underlying mechanisms of lentivirus-mediated human tissue kallikrein gene transfer in myocardial fibrosis in VMC mice. We established VMC mouse model via intraperitoneal injection with Coxsackie B3 virus. The effect was then assessed after treatment with vehicle, the empty lentiviral vectors (EZ.null), and the vectors expressing hKLK1 (EZ.hKLK1) via tail vein injection for 30 days, respectively. The results showed that administering EZ.hKLK1 successfully induced hKLK1 overexpression in mouse heart. Compared with EZ.null treatment, EZ.hKLK1 administration significantly reduced the heart/weight ratio, improved cardiac function, and ameliorated myocardial inflammation in VMC mice, suggesting that hKLK1 overexpression alleviates VMC in mice. EZ.hKLK1 administration also significantly abrogated the increased myocardial collagen content, type I/III collagen ratio, TGF-β1 mRNA and protein expression in VMC mice, suggesting that hKLK1 overexpression reduces collagen accumulation and blunts TGF-β1 signaling in the hearts of VMC mice. In conclusion, our results suggest that hKLK1 alleviates myocardial fibrosis in VMC mice, possibly by downregulating TGF-β1 expression.

Keywords: Human tissue kallikrein; Myocardial fibrosis; Myocardial inflammation; Transforming growth factor β1; Viral myocarditis

Grants and funding:

This work was supported by Scientific Research Project of Traditional Chinese Medicine Bureau of Guangdong Province, China (No. 20171273; No. 20201368); Medical Scientific Research Foundation of Guangdong Province, China (No. B2017033); and Dongguan Science and Technology Bureau, China (No. 202071715024129); Medical Scientific Research Foundation of Guangdong Province, China (No. B2022026).

Conflicts of interest:

The authors have no conflict of interests to declare.

Received: April 21, 2022; Revised: February 2, 2023; Accepted: March 24, 2023; Prepublished online: April 3, 2023; Published: April 1, 2023 Show citation

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