Action of the Gremlin gene on the profile of monocytes and macrophages in the progression of atherosclerosis

• Grant number: 18/15976-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2019
• End date: March 31, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Alexandre Holthausen Campos
• Grantee: Daniela Harsanyi
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil

Abstract

The development of atherosclerosis involves the activation and modification of various cell types, such as vascular smooth muscle cells (VSMC), endothelial cells and cells of the immune system. Genes such as BMPs and their antagonist Gremlin are related to the pathophysiology of this disease. To investigate this, we established a line of mice susceptible to plaque formation and gaining BMPs function by partial loss of their antagonist (Gremlin+/- ApoE-/-). We observed that, when fed for 16 weeks on a hyperlipidemic diet, the Grem+/- ApoE -/- mice had a lower mass of atherosclerotic plaques in the aorta and a reduced number of myeloid cells when compared to the ApoE -/- mice. In the pathophysiology of atherosclerosis, monocytes and macrophages are cells of special interest, due to their participation in both the onset and progression of the disease. It is known that these cells are capable of assuming different phenotypes according to the stimuli that they receive from the microenvironment: M1 macrophages are predominantly pro-inflammatory and M2 are anti-inflammatory. Therefore, we will investigate if the differences observed in the atheroma plaque of the Grem +/- ApoE -/- animals may be related to their macrophages/monocyte profile.