Cholesterol-lowering agents, such as the widely-prescribed statin drugs, and cholesterol-blocking agents may prove to be “novel therapeutic agents to modify cellular calcium that contributes to the development of pulmonary hypertension,” according Hemal H. Patel who lead a multidisciplinary team of researchers at the University of California, San Diego (UCSD).
In studying idiopathic pulmonary hypertension (PPH), formerly called primary pulmonary hypertension, the UCSD team found “a previously unappreciated cellular and molecular mechanism for the disease process,” Patel said, “which may be amenable to treatment with current and future therapies and might provide more substantial, long-term and efficacious benefit to those that have IPAH.”
Patel is presenting the research at the 35th Congress of the International Union of Physiological Sciences in San Diego, March 31 - April 5, 2005.
All researchers involved in the study are from UCSD: Hemal H. Patel, Fiona Murray and Paul A. Insel, Department of Pharmacology; Shen Zhang and Jason X-J Yuan, Dept. of Medicine, and Patricia A. Thistlethwaite, Dept. of Surgery.
Research aimed at cellular calcium-dependent aspects of hypertension
IPAH is a severe clinical disease. The prognosis of PPH is poor with untreated disease leading to heart failure and death in two to eight years, Patel noted. Because of limited 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