IUPS/APS Newsroom March 29-April 6
San Diego Convention Center
Hall E Registration Area/Flex Unit
Telephone: 619.525.6228
Contact: Donna Krupa
(703) 967-2751 (cell)
(301) 634-7209 (office, outside IUPS dates)
Statins, Other
Cholesterol-depleting Agents, May Disrupt Hypertension from Developing, UCSD
Researchers Say
San Diego (April 3, 2005) – 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.
*Paper presentation: “Cholesterol-depleting
drugs, including statins, lower intracellular Ca2+ and inhibit proliferation
in pulmonary artery smooth muscle cells in primary pulmonary hypertension,”
12:30 p.m.-3 p.m. Tuesday April 5, Physiology 933.6/board #A446. On view
7:30 a.m. - 4 p.m.
*Featured topic: Patel will participate in
Session 898, “Overview: From organelles to organ,” a featured topic of the
IUPS Calcium Signaling Track, Tuesday beginning at 10:30 a.m., Convention
Center room 29C. Patel’s presentation is scheduled for noon.
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
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 increased calcium intake in
IPAH,” Patel stated.
Next steps: Determine caveolae proteins and how they
influence calcium intake
The next steps, Patel explained, are to understand the
nature of the proteins located on the caveolae and how these structures
communicate with the internal regions of cells to influence calcium intake
into the cell. He said the UCSD researchers “already have begun looking at
the expression and localization of ion channels into caveolae that may
further explain the increased calcium intake into cell.”
Funding. The research in the study was supported
by the National Institutes of Health.
***
The 35th Congress of the International Union of
Physiological Sciences is in San Diego, March 31 - April 5, 2005. The
Congress (http://www.iups2005.org/)
is organized by the six member societies of the U.S. National Committee of
the IUPS,
the American Physiological Society,
the Society for Neuroscience,
the Microcirculatory Society,
the Society of General Physiologists,
the Biomedical Engineering Society, and
the Society for Integrative and Comparative Biology, under the auspices
of the U.S. National Academy of Sciences.
The IUPS conference, held every four years, runs
concurrently this year with Experimental Biology 2005 at the San Diego
Convention Center.
The American Physiological Society (APS), which is
hosting IUPS, was founded in 1887 to foster basic and applied science, much
of it relating to human health. The Bethesda, MD-based Society has more than
10,000 members and publishes nearly 4,000 articles every year in its 14
peer-reviewed journals. In May, APS received the Presidential Award
for Excellence in Science, Mathematics and Engineering Mentoring (PAESMEM).
***
Editor’s Note: For further information or to
schedule an interview with a member of the research team, please contact
Donna Krupa at the IUPS/APS newsroom @ 619.525.6228 (March 31-April
6), or (703) 967-2751 (cell) or (301) 634-7209 (office), or Stacy Brooks at
240.432.9697 (cell) or 301.634.7253 (office).
A searchable online program for IUPS and EB is at
http://www.faseb.org/meetings/eb2005/call/default.htm
