Apolipoprotein A-I mimetic peptide L-4F prevents myocardial and coronary dysfunction in diabetic mice

C. Vecoli, J. Cao, D. Neglia*, K. Inoue, K. Sodhi, L. Vanella, K. K. Gabrielson, D. Bedja, N. Paolocci, A. L'Abbate, N. G. Abraham

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Diabetes is a major health problem associated with adverse cardiovascular outcomes. The apolipoprotein A-I mimetic peptide L-4F is a putative anti-diabetic drug, has antioxidant and anti-inflammatory proprieties and improves endothelial function. In obese mice L-4F increases adiponectin levels, improving insulin sensitivity, and reducing visceral adiposity. We hypothesized that the pleiotropic actions of L-4F can prevent heart and coronary dysfunction in a mouse model of genetically induced Type II diabetes. We treated db/db mice with either L-4F or vehicle for 8 weeks. Trans-thoracic echocardiography was performed; thereafter, isolated hearts were subjected to ischemia/reperfusion (IR). Glucose, insulin, adiponectin, and pro-inflammatory cytokines (IL-1β, TNF-α, MCP-1) were measured in plasma and HO-1, pAMPK, peNOS, iNOS, adiponectin, and superoxide in cardiac tissue. In db/db mice L-4F decreased accumulation of subcutaneous and total fat, and increased insulin sensitivity and adiponectin levels while lowering inflammatory cytokines (P<0.05). L-4F normalized in vivo left ventricular (LV) function of db/db mice, increasing (P<0.05) fractional shortening and decreasing (P<0.05) LV dimensions. In I/R experiments, L-4F prevented coronary microvascular resistance from increasing and LV function from deteriorating in the db/db mice. These changes were associated with increased cardiac expression of HO-1, pAMPK, peNOS, and adiponectin and decreased levels of superoxide and iNOS (P<0.01). In the present study we showed that L-4F prevented myocardial and coronary functional abnormalities in db/db mice. These effects were associated with stimulation of HO-1 resulting in increased levels of anti-inflammatory, anti-oxidative, and vasodilatatory action through a mechanism involving increased levels of adiponectin, pAMPK, and peNOS.

Original languageEnglish
Pages (from-to)2616-2626
Number of pages11
JournalJournal of Cellular Biochemistry
Volume112
Issue number9
DOIs
Publication statusPublished - Sep 2011
Externally publishedYes

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