Introduction: Cardiovascular diseases (CVDs) are a set of disorders combined with vascular and cardiac functions such as cerebrovascular disease, angina, atherosclerosis, coronary heart disease, myocardial infarction, and heart failure. CVDs are the most important cause of mortality and morbidity in both developing and developed countries. While acute inflammation is a process that protects tissues, it’s becoming chronic and causes various pathologies. CVDs are a chronic inflammatory process. Pro-inflammatory cytokines such as IL-1β, IL-6, IL-17, IL-18, IL-21, IL-33, and TNF-α also trigger pathological disease, however, anti-inflammatory cytokines such as IL-10 and TGF-β reduce inflammation. MOTS-c is a mitochondrial-derived peptide encoded from 12S rRNA in mitochondrial DNA and referred to as the mitochondrial open reading frame of 12S Rna-type c. MOTS-c regulates metabolic pathways such as insulin sensitivity, glucose, and lipid homeostasis. It is stated that MOTS-c has a protective role in the progression of diabetes, cardiovascular disease, inflammation, osteoporosis, aging, and lung injury. However, few studies have investigated the effects of MOTS-c on inflammation.

Objective: We aimed to investigate how MOTS-c affects inflammatory cytokine levels after abdominal aortic constriction (AAC) induced cardiac hypertrophy.

Method: For this purpose, twenty-eight male Wistar albino rats grouped as (aged 2 months ) sham+saline (saline;1 ml/kg, n=6), sham+MOTS-c (MOTS-c;5 mg/kg,n=6), AAC+saline( Saline;1 ml/kg,n=8) and AAC+MOTS-c (MOTS-c;5 mg/kg,n=8). Cardiac hypertrophy models were induced by abdominal aortic ligation by using 4.0 silk sutures (Marano G,et al., 2002). Following the formation of the AAC model for 14 days, treatments were administered intraperitoneally for 21 days. Under ketamine+xylazine (100 mg/kg+15 mg/kg; i.p) anesthesia the rats were sacrificed and serum and tissue samples were taken. Histopathological analyses were performed with hematoxylin-eosin, Masson's trichrome, and Toluidine blue in the thoracic and abdominal aorta and heart tissue. The mRNA expressions of IL-1β, IL-18, TGF-β, and TNF-α genes involved in the inflammatory process in both the left ventricle of the heart and abdominal aorta tissues were determined by qPCR. Data were given as mean ± standard error, statistical analysis was compared with t-tests in independent groups. All experiments were performed in accordance with the "Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals prepared by the Adiyaman University, Animal Ethical Committee"( Turkey (Approved date 04.11.2022, no;2021/030).

Result: Histopathological analyses showed that the abdominal aortic tissue deteriorated in the AAC+saline group, while the vessel wall structure of the AAC+ MOTS-c treatment group was preserved.

mRNA expressions of IL-1β, IL-18, TGF-β, and TNF-α in aortic tissue were not a significant difference between the AAC and sham groups, but IL-1β, IL-18, TGF-β1, and TNF-α were upregulated in the AAC+MOTS-c group compared to the AAC group. Similarly, no difference in gene expression of IL-1β, IL-18, and TNF-α in heart tissue was observed between the AAC and sham groups, however, downregulated TGF-β1 levels. Conversely, IL-18 and TGF-β1 levels were approximately increased 10-fold in the AAC+MOTS-c group compared to the AAC group.

Conclusion: Our study revealed that inflammatory response genes were regulated by MOTS-c peptides. This peptide may have protective effects on cardiovascular damage progression.