丁香园AV

The stimulation of blood vessels by sympathetic nerves is a primary regulator of vascular tone. While these nerves are best known for stimulating contraction by releasing norepinephrine, they also release co-transmitters like ATP, neuropeptide Y, and beta-nicotinamide adenine dinucleotide. I am interested in the mechanisms that regulate which of these neurotransmitters are released, and how such 鈥渃o-release鈥� can be altered physiologically, as well as how they contribute to vascular pathologies like hypertension. We employ fluorescence microscopy, wire myography, and other molecular techniques to examine how ATP and norepinephrine are differentially stored and released from sympathetic nerve endings in rat blood vessels. We are also developing novel molecular probes to directly, and for the first time, monitor the release of ATP from individual synaptic varicosities, and are developing novel assays to image the release of synaptic vesicles in intact blood vessels. 

High blood pressure is a major risk factor for cardiovascular disease, the leading cause of death in the developed world. Two common causes of high blood pressure are the narrowing of blood vessels due to excess vasoconstriction and the thickening of vascular walls due to smooth muscle proliferation (i.e. remodelling). There is growing recognition that both acute and chronic formation of mitochondrial dysfunction promotes vascular remodeling, and affects vascular smooth muscle contractility and phenotype. In this regard, mitochondria are a common target of chronic inflammation, stress, diabetes and obesity. My lab is using cell and organ cultures to examine how noxious stimuli commonly experienced by blood vessels impact mitochondrial health, and how this affects smooth muscle phenotype and cell cycle. We employ high content imaging assays, wire myography, molecular analyses of gene transcription, and mitochondrial DNA modification to better understand the interplay between mitochondrial dysfunction and its impact on smooth muscle physiology.