Adropin and Spexin Peptides Ameloriate Cardiac Inflammation, Matrix Metalloproteinases, and Vascular Response.

Abstract

Background: Chronic renal failure (CRF) triggers chronic systemic inflammation and causes vascular calcification, a prominent contributor to the progression of cardiovascular disease. Adropin and spexin peptides regulate energy balance; also, these peptides trigger anti-inflammatory pathways.

Objective: Our present study aimed to clarify the potentially protective impact of spexin and adropin peptides on cardiovascular inflammation in an adenine-induced chronic renal failure model.

Methods: The CRF model in Sprague-Dawley rats was established by the administration of adenine hemisulfate for ten days. Then, rats were treated with saline or adropin, or/and spexin for four weeks. CRP, CK, and CK-MB levels in serum were measured by autoanalyzer. Aortic contraction- relaxation responses were determined by the organ bath system. H&E, PAS, and Masson's trichrome stainings evaluated histopathological alterations in both aorta and cardiac tissue. Gene expression levels of ILs (IL1β, IL10, IL17A, IL18, IL21, and IL33), MMPs (MMP1, MMP2, MMP3, MMP9, MMP13, and MMP14), NGAL, TGFβ1, TIMP1, and TNFα in cardiac tissue were evaluated by real-time PCR.

Results: We found increased CK and CK-MB levels by CRF induction. In addition, IL1β, IL17A, IL18, IL21, MMP1, MMP3, MMP13, and MMP14 increased after CRF progression. While adropin has effects on CK levels, spexin decreases CK-MB levels. Also, adropin and spexin had a nitric oxide-dependent impact on vascular reactivity. Besides, spexin downregulated IL1β, IL10, IL17A, TGFβ1, MMP1, MMP3, MMP9, MMP13, MMP14 and NGAL; however, the adropin peptide had a limited effect.

Conclusion: These results suggest that adropin and spexin have potential preventive roles on vascular damage in CRF progression via modulation of MMPs and inflammatory genes.