Elsa I. Mangiarua
Associate
Professor
Ph.D., University of Buenos Aires, 1983.
Research Interests:
Cardiovascular physiology.
Vascular changes during the development of hypertension.
Effects of vasoactive substances and cyclic stretch on vascular
smooth muscle growth.
Description of Research:
Our research is designed to explore the pathophysiological
mechanisms leading to the development of vascular structural
changes in hypertension. While the description of the vascular
changes in hypertension is extensive in the literature, the
mechanisms responsible for them are poorly understood. Genetic,
humoral, nervous and hemodynamic factors have been postulated. We
are interested in studying the effects of humoral and hemodynamic
factors on vascular smooth muscle growth. We have shown that
angiotensin II induces proliferation of vascular smooth muscle
cells in culture and that the effect may be mediated by
platelet-derived growth factor. Our previous research has also
provided strong evidence indicating that mechanical factors
induce biochemical changes in vascular smooth muscle. Using an in
vitro organ culture system, we showed that an increase in
intraluminal pressure in perfused rat aorta increases DNA
synthesis and the expression of c-fos, a protooncogene known to
be involved in cell proliferation. These results suggest that
mechanical loading may directly increase cell growth and
proliferation. Further work is needed to elucidate the precise
mechanisms of how hemodynamic and/or mechanical stimuli are
converted into biochemical signals that lead to changes in gene
expression. Our current projects are aimed at providing new
information regarding the signal transduction pathways initiated
by mechanical stimuli and leading to DNA synthesis in cultured
vascular smooth muscle cells. We are examining the contribution
of c-fos protooncogene to the mitogenic effect of cyclic
stretching and the participation of protein kinase C (PKC)
activation in the cellular response to cyclic stretching. Taken
together, these studies will broaden our knowledge of the signal
mechanisms in response to mechanical factors in vascular smooth
muscle cells.
Recent publications:
Mangiarua EI, Galagedera NJ, Patterson JR. Increased intraluminal pressure induces DNA
synthesis and c-fos expression in perfused rat aorta. Archives of
Physiology and Biochemistry 104:838-844,1996.
McCumbee WD, Hickey VL, Lloyd LL, Mangiarua EI. Interactions between angiotensin II and adenosine
3':5'-cyclic monophosphate in the regulation of amino acid
transport by vascular smooth muscle cells. Canadian Journal of
Physiology and Pharmacology 74:173-181,1996.
Mangiarua EI, Palmer VL, Lloyd LL, McCumbee WD. Platelet-derived growth factor mediates angiotensin
II-induced DNA synthesis in vascular smooth muscle. Archives of
Physiology and Biochemistry 105:151-157,1997.