Xi-Long Zheng

Vascular Smooth Muscle and Human Diseases
Proliferation of vascular smooth muscle cells (SMCs) is a key event in the development of atherosclerosis, which has been known for many years. However, the exact mechanisms remain to be addressed. In this project, we are trying to understand whether and how mature SMCs contribute to this proliferative vascular disease, and if other non-mature muscle cells within the blood vessel wall also contribute to the development of the lesions. It is also our interest to investigate how proliferative SMCs develop into foam cells containing excessive cholesterols in atherosclerotic lesions. The ultimate goal is to define cellular and molecular targets for the development of therapeutic approaches.

Early studies revealed similarities between SMC proliferation in the blood vessel with that in human uterine leiomyoma, a benign smooth muscle tumor. Therefore, we are also interested in understanding why myometrial SMCs undergo abnormal proliferation.

At the molecular level, we have been focusing on several compounds and proteins as listed below.

Tuberin 
Tuberin is the gene product of tuberous sclerosis complex (TSC)-2 and has GTPase activating protein (GAP) functions. Malfunction of tuberin due to either mutation or deficiency results in a condition called tuberous sclerosis complex, a rare multi-system genetic disease, which is accompanied by proliferation of vascular SMCs in renal angioleiomyomas. Therefore, we are trying to understand how tuberin is involved in the regulation of smooth muscle functions including the cell cycle.

Phospholipase D (PLD) 
In response to various stimuli, PLD hydrolyzes the phosphodiester bond of the glycerolipid phosphatidylcholine to generate phosphatidic acid and free choline, which likely regulate the cell cycle. We are interested in how PLD activation stimulates proliferation and migration of vascular SMCs.

Myocardin
As a co-transcriptional factor of serum response factor, myocardin specifically stimulates the expression of smooth muscle contractile proteins. Our recent studies have revealed inhibitory effects of myocardin on the cell cycle. We are interested in understanding how myocardin directs the differentiation of stem cells.

Uridine adenosine tetraphosphate (Up4A)
Up4A is a novel endothelium-derived contraction factor that potently stimulates proliferation of human vascular SMCs. The plasma concentration of Up4A is significantly elevated in juvenile hypertensive patients. We are interested in further understanding its roles in the pathogenesis of hypertension and atherosclerosis.

2-Methoxyestradiol (2-ME)
2-ME is an estrogen metabolite with significant effects on the smooth muscle cell cycle. It causes mitotic apoptosis of human vascular SMCs. Our recent studies revealed its inhibitory effect on the development of hypertension in rats. We wish to understand more about the mechanism behind this effect and hope to develop analogs for specific clinical diseases.

Research Areas: 

Molecular Biology and Disease

Research Personnel: 

• Stephanie Howe, Graduate Student
• Xiaopu Wang, Graduate Student
• Fatemeh Hashemi, Graduate Student
• Musstafa Smeir, Graduate Student
• Katayoun Heshmatzad, Graduate Student
• Roasan Gonzalez Granado,Student
• Binjie Yan, Visiting Scholar
• Junyu Pei,  Visiting Scholar 
• Jiaxing Sun, Visiting Scholar
• Lilibeth Alcantara, Administrative Assistant