- COUNTRY USA
Our laboratory is addressing two of the most important issues in vascular biology today: stroke mechanisms; and irreversible cellular destruction in the cardiovascular system caused by alcohol and substance abuse. These studies have already led to the prevention of atherosclerotic lesions, hypertension and stroke-like events in experimental animal models. Additional experimental studies, using manipulations in divalent cation metabolism, have been very effective in the prevention and amelioration of alcohol-, phencyclidine-, cocaine-, and other substance abuse-induced strokes.
We are using intact animals, isolated organs, tissues and cells in culture to understand how divalent cations (Mg2+ and Ca2+), sphingolipids, lipid messengers, protein kinase C and nuclear transcription factors control normal fuctions of vascular smooth muscle cells, cardiac myocytes and several types of neuronal cells. In order to accomplish these goals, we employ various state-of-the-art techniques: NMR spectroscopy; in-vivo high-resolution TV microscopy; digital image microscopy; confocal laser scanning microscopy; culture of primary cells; Mg2+ ion-selective electrodes; mono- and polyclonal antibodies; antisense oligonucleotides; and lipid chemistry. Use of the various models and techniques has led us to hypothesize that magnesium ions can regulate voltage-, receptor-, and leak-operated membrane channels in a number of cell types and that various cellular signaling pathways, particularly isoforms of PKC and sphingolipids are turned on or off by the actions and concentrations of Mg2+ at multiple cellular sites.