Vasoactive intestinal peptide (VIP) is a
neuropeptide that exerts various vascular and cardioprotective functions and regulates immune function and inflammatory response at multiple levels. However, its role in inflammatory cardiovascular disorders is largely unknown.
Myocarditis and
atherosclerosis are two inflammatory and autoimmune
cardiovascular diseases that cause important adverse circulatory events. In this study, we investigate the
therapeutic effects of VIP in various well-established preclinical models of experimental autoimmune
myocarditis and
atherosclerosis.
Intraperitoneal injection of VIP during the effector phase of experimental autoimmune
myocarditis in susceptible BALB/c mice significantly reduced its prevalence, ameliorated signs of
heart hypertrophy and injury, attenuated myocardial inflammatory infiltration, and avoided subsequent profibrotic cardiac remodeling. This effect was accompanied by a reduction of Th17-driven cardiomyogenic responses in peripheral lymphoid organs and in the levels of myocardial
autoantibodies. In contrast, acute and chronic
atherosclerosis was induced in
apolipoprotein E-deficient mice fed a hyperlipidemic diet and subjected to partial carotid
ligation. Systemic VIP treatment reduced the number and size of
atherosclerotic plaques in carotid, aorta, and sinus in hypercholesterolemic mice. VIP reduced Th1-driven inflammatory responses and increased regulatory T cells in atherosclerotic arteries and their draining lymph nodes. VIP also regulated
cholesterol efflux in macrophages and reduced the formation of foam cells and their presence in
atherosclerotic plaques. Finally, VIP inhibited proliferation and migration of smooth muscle cells and
neointima formation in a mouse model of complete carotid
ligation. These findings encourage further studies aimed to assess whether VIP can be used as a
pharmaceutical agent to treat heart
inflammation and
atherosclerosis.