Molecular and Genetic Cardiovascular Pathophysiology

The World Health Organization has estimated that cardiovascular disease (CVD) will by 2020 be the main health and socio-economic problem worldwide, in part due to the progressive aging that the world population is experiencing. Atherosclerosis and heart failure contribute significantly to CVD-related morbimortality in the elderly. These anomalies and the aging process are much accelerated in Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder caused by the expression of progerin, a mutant form of lamin A. The most serious aspect of HGPS is extensive atherosclerosis and cardiac electrophysiological alterations which are associated with early death (average lifespan: 13.5 yr, range: 8-21 yr), predominantly from myocardial infarction or stroke. Progerin is also expressed at low level in aged tissues of non-HGPS individuals, suggesting a role in normal aging. Understanding how this mutant form of lamin A causes CVD and premature aging may therefore shed light on normal aging.

Our research currently focuses on:

  1. Identifying mechanisms through which wild-type lamin A/C regulate CVD.
  2. Identifying tissue-specific and systemic mechanisms through which progerin promotes atherosclerosis and aging, and develop novel therapeutic strategies.
  3. Generating a porcine model of HGPS using the CRISPR/Cas9 technology to accelerate translational research in HGPS.
  4. Unraveling molecular mechanisms common to premature and physiological aging and specific to each process.