Aims

Rigorous human evidence is the central premise of our proposal. Given the complexity of cellular pathology, the profound temporal changes in risk profiles, the preventive treatment of patients, and the underlying pathological substrate, we assert that evidence from human observations is key to the identification of regulatory mechanisms that determine plaque destabilization and stabilization.

Such evidence will further be complemented through validation in both human in vitro and preclinical cellular and animal model studies.





Aim 1

Define molecular markers of SMC and ECM phenotypes that associate with de-stabilization and stabilization of human atherosclerotic lesions


Aim 2

Employ integrative systems genetics to identify gene networks and within these, pathways that induce detrimental reprogram-ming of SMC and/or other ECM producing cells that contribute to plaque destabilization


Aim 3

Define the key drivers of SMC reprogramming that impact plaque stabilization and destabilization.