Kathleen A Martin PhD

Associate Professor of Medicine (Cardiology)

Research Interests

vascular smooth muscle; differentiation; signal transduction; transcription; translation

Research Summary

Our studies are aimed at understanding the molecular mechanisms that regulate vascular smooth muscle cell (SMC) phenotype. Mature SMC retain the ability to de-differentiate and re-enter the cell cycle. This is essential for such processes as angiogenesis, but also contributes to the pathogenesis of atherosclerosis, intimal hyperplasia, and restenosis.

Rapamycin/mTOR and adiponectin signaling: Rapamycin-eluting stents have revolutionized treatment of coronary artery disease, dramatically reducing restenosis. However, drug-eluting stents have recently been associated with an increased risk of late stent thrombosis, a potentially fatal complication. Delayed healing of the endothelium in response to these drugs may contribute to this effect. Our goal is to understand the mechanisms by which rapamycin beneficially affects SMC phenotype, in order to develop novel ways to achieve this end without endothelial inhibition. Identifying the smooth muscle-specific targets of the mTOR pathway may generate new therapeutic strategies for treatment and prevention of atherosclerosis and intimal hyperplasia.

We have recently demonstrated that the fat-derived cardioprotective hormone adiponectin inhibits mTOR and promotes differentiation in VSMC, analogous to rapamycin. In contrast to rapamycin, adiponectin has many beneficial effects on vascular endothelium. We are also investigating the effects of secondhand smoke exposure on adiponectin, mTOR signaling, and vascular disease.

Prostacyclin regulation of smooth muscle contractile proteins: Our laboratory also studies how prostacyclin, an endothelial-derived prostaglandin product of COX-2, promotes vascular SMC differentiation (in collaboration with Dr. John Hwa). These studies have identified a novel mechanism underlying prostacyclin’s cardioprotective effects, which may contribute to the adverse cardiovascular events associated with COX-2 inhibitors such as rofecoxib (Vioxx). These observations have led us to another exciting project in studying the role of prostacyclin in regulating contraction and induction of labor in human uterine smooth muscle.

Extensive Research Description

Our studies are aimed at understanding the molecular mechanisms that regulate vascular smooth muscle cell (SMC) phenotype. Mature SMC retain the ability to de-differentiate and re-enter the cell cycle. This is essential for such processes as angiogenesis, but also contributes to the pathogenesis of atherosclerosis, intimal hyperplasia, and restenosis.

Rapamycin/mTOR and adiponectin signaling: Rapamycin-eluting stents have revolutionized treatment of coronary artery disease, dramatically reducing restenosis. However, drug-eluting stents have recently been associated with an increased risk of late stent thrombosis, a potentially fatal complication. Delayed healing of the endothelium in response to these drugs may contribute to this effect. Our goal is to understand the mechanisms by which rapamycin beneficially affects SMC phenotype, in order to develop novel ways to achieve this end without endothelial inhibition. Identifying the smooth muscle-specific targets of the mTOR pathway may generate new therapeutic strategies for treatment and prevention of atherosclerosis and intimal hyperplasia.

We have recently demonstrated that the fat-derived cardioprotective hormone adiponectin inhibits mTOR and promotes differentiation in VSMC, analogous to rapamycin. In contrast to rapamycin, adiponectin has many beneficial effects on vascular endothelium. We are also investigating the effects of secondhand smoke exposure on adiponectin, mTOR signaling, and vascular disease.

Prostacyclin regulation of smooth muscle contractile proteins: Our laboratory also studies how prostacyclin, an endothelial-derived prostaglandin product of COX-2, promotes vascular SMC differentiation (in collaboration with Dr. John Hwa). These studies have identified a novel mechanism underlying prostacyclin’s cardioprotective effects, which may contribute to the adverse cardiovascular events associated with COX-2 inhibitors such as rofecoxib (Vioxx). These observations have led us to another exciting project in studying the role of prostacyclin in regulating contraction and induction of labor in human uterine smooth muscle.

Selected Publications