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Statins, other cholesterol depletors, may disrupt hypertension development: UCSD study

ted understanding of the cellular and molecular determinants of the disease process, current therapy is limited and aimed towards symptomatic relief.

He said two factors that contribute to the disease are dependent on cellular calcium: constriction of vessels, and uncontrolled cell growth resulting in thickening of vessels. "We sought to determine, 1.) if IPAH has altered caveolae, which in Latin means "little caves," on the membrane composed of cholesterol that control the intake of calcium into cells, and 2.) if agents that modify cellular cholesterol might limit calcium intake and ultimately limit the two factors (constriction and growth) in vessels that contribute to the disease process. These drugs then might provide for a novel therapy that not merely provides temporary relief of disease symptoms, but helps alleviate the underlying cause of IPAH," Patel explained.

Lovostatin, MBCD significantly reduce calcium entry, cut cell proliferation

In their research, the team saw that "smooth muscle cells isolated from pulmonary arteries of patients with IPAH indeed had more caveolae on the cell membrane compared to cells from normal individuals, and also that there was a higher calcium intake into the diseased cells," Patel reported. Subsequent treatment of the IPAH cells with an agent that depletes cholesterol (methyl-beta-cyclodextrin, or MBCD), or "a statin (in this case, lovostatin, sold as Mevacor by Merck), which blocks cholesterol synthesis, resulted in a disruption of the caveolae and reduced the amount of calcium that entered the cells.

"Additionally, these two treatments also decreased the growth rate of the diseased cells," Patel said. Taken together, the results "mean that the micro-structure of the cell membrane is involved in controlling the intake of calcium and that the cholesterol modifiers of these structures may serve as novel therapeutics to reduce vessel constriction and cell growth associated with increase
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3-Apr-2005


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