Docosahexaenoic acid nanoencapsulated with Anti-Pecam-1 as strategy to increase atherosclerotic plaque stability

• Grant number: 21/02021-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2021
• End date: May 31, 2022
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Inar Castro Erger
• Grantee: Isabella di Piazza
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiovascular disease is the leading cause of mortality in many countries. Atherosclerosis is a chronic inflammation of the arteries that underlies the ischemic events involved in myocardium infarction and stroke. Although important advances had been developed in terms of atherosclerosis prevention, more recent strategies have focused on plaque regression or stability. The atherosclerotic plaque, formed in the intima layer of the endothelium, mainly consists of lipid-rich macrophages (foam cells) surrounded by vascular smooth cells and extracellular matrix. Plaques that present a higher inflammation level are more susceptible to suffer micro-hemorrhage, fissure, and rupture, forming a thrombus able to occlude the arterial blood vessel, causing the ischemic events. Docosahexaenoic acid is a natural compound that promotes anti-inflammatory effects by different physiological mechanisms, including enzymatic oxidation that produces molecules known as resolvins, involved in the inflammation resolution and maybe efferocytosis. Although several studies have pointed out the beneficial effects of DHA on inflammation, results are still controversial when endpoints, such as atherosclerotic plaques are taken into account. One reason for the little evidence of these potential effects has been attributed to the chemical alterations that polyunsaturated fatty acids can suffer until they achieve the endothelium, where the plaque is being formed. For this reason, the objective of this study is to develop a nanocapsule vectorized with anti-Pecan 1 containing DHA inside its lipid core. LDLr(-/-) mice will be divided into 4 groups and kept for 24 weeks under a Western diet in order to develop lesions in the aortic root. After this period, one group will receive algae oil in the diet (DHA-D), the other two groups will be injected once a week with DHA-anti-Pecam 1 nanocapsules (DHA-APNC) or anti-Pecam 1 nanocapsules (APNC), and the last group will not receive any treatment (CONT). After 8 weeks, the animals will be euthanized and biological samples will be collected and kept at -80oC for future analysis. Basically, inflammatory cytokines, oxidative stress markers, dyslipidemia parameters, and immune cells profile will be analyzed. The end-point of the study will be the lesion area determined by histological and CT-PET methods. Results from this study will contribute to defining strategies that combine nutrients and drugs aiming to regress or stabilize atherosclerotic plaques. (AU)