Project 1


Social stress is a risk factor for atherosclerotic disease. Atherosclerosis, the underlying cause of myocardial infarction and stroke, is a lipid-driven chronic inflammatory disease characterized by lipoprotein and leukocyte accumulation in the vessel wall.  Among leukocytes, monocyte-derived intimal macrophages are arguably the most decisive contributors to the development, progression, exacerbation, and regression of atherosclerosis. As key effectors of inflammation, proteolysis, oxidative stress, lipid clearance, and efferocytosis, macrophages have long been therapeutic targets for the treatment of atherosclerosis.

Recently, we showed that psychosocial stress, which potentiates cardiovascular disease, aggravates atherosclerosis by disturbing the macrophage supply chain; animals subjected to intermittent psychosocial stress developed by inflamed lesions containing more numerous macrophages than controls. This Project will investigate how social stress affects macrophage dynamics in atherosclerosis, with specific focus on the sympathetic nervous system and neuronal guidance cues.  By utilizing the ApoE-/- mouse model of atherosclerosis, we are more closely mimicking the clinical setting of a patient with chronic inflammation (atherosclerosis).  This research will be conducted at NYU and MGH.

Specific Aims:

  • Aim 1: To identify the underlying mechanisms controlling macrophage dynamics and quantify their relative contributions to the progression of atherosclerosis during stress
  • Aim 2: To decipher macrophage dynamics in the regression of atherosclerosis during stress