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Cholesterol Therapy Could be Beneficial For PH Patients
by John C. Martin
04-14-05 - Medications currently prescribed to reduce high levels of cholesterol could have beneficial implications for people diagnosed with pulmonary hypertension, according to doctors in California.
The drugs, including those known as statins, may "modify cellular calcium that contributes to the development of pulmonary hypertension," says Hemal Patel, PhD, a postdoctoral researcher in the department of Pharmacology at the University of California-San Diego, and the study's chief investigator.
Patel and a team of medical researchers presented their findings at a meeting of the International Union of Physiological Sciences in San Diego earlier this month.1
Skyrocketing Blood Pressure
Pulmonary hypertension is a fairly rare disorder of the blood vessels that feed the lungs. When it strikes, the blood pressure in the pulmonary artery—running from the heart to the lungs—rises above normal levels and can become life threatening. There are two types of pulmonary hypertension. Primary pulmonary hypertension is diagnosed in people without a known cause. It is extremely rare, occurring in approximately 2 people for every million each year.
Secondary pulmonary hypertension, on the other hand, can be caused by any number of factors, including the breathing disorders emphysema and bronchitis (known collectively as chronic obstructive pulmonary disease (COPD)); or inflammatory or collagen vascular diseases like scleroderma, CREST syndrome, or systemic lupus erythematosus (SLE). Other causes include certain forms of congenital heart diseases, chronic pulmonary thromboembolism (old blood clots in the pulmonary artery), HIV infection, and liver disease.
Often, PH can be misdiagnosed and may not be discovered until it has reached its later stages. But the development of new treatments for the disease has improved people's odds of survival.2
Still, because of the limited understanding of the underlying cellular and molecular processes involved in the development of the disease, treatment is also currently limited and aimed mostly at improving symptoms, according to the International Union of Physiological Sciences.
Do Cholesterol Blockers Work in PH?
In their study of the mechanisms that make up primary PH, Patel's team discovered that two factors that contribute to the disease—blood vessel constriction and uncontrolled cell growth that thickens blood vessels—primarily rely on calcium found in cells.
Among other things, they wanted to find out if drugs that limit cholesterol intake might also block calcium from entering cells, which in turn, would help inhibit blood vessel narrowing and thickening characteristic of pulmonary hypertension. That's because membranes found on cells are made of cholesterol, and control how much calcium is collected by the cell.
If their theory proved correct, it might lead to medications that don't just control the symptoms of pulmonary hypertension, but treat the underlying disease itself.
Distinct Differences Found
For their study, the researchers examined a collection of smooth muscle cells—those that line the inside of blood vessels and play a key role in collecting calcium which leads to blood vessel narrowing and thickening. When they compared the cells of people with PH to the cells of people without the disease, they found that those taken from the PH group tended to collect calcium in higher amounts. "There was a higher calcium intake into the diseased cells," Patel's group wrote.
Next, they wanted to find out if using a cholesterol-lowering drug might make a difference. They tried two medications: methyl-beta-cyclodextrin (MBCD) and Mevacor (lovostatin), a statin drug currently available to people with high cholesterol. They found that the drugs were, in fact, effective at blocking the smooth muscle cells' ability to take up calcium.
Other Benefits of the Medications
"Additionally, these two treatments also decreased the growth rate of the diseased cells," explained Patel. 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 [primary pulmonary hypertension]."
Patel's group next wants to take their research even deeper, studying how proteins located on the cholesterol membranes of smooth muscle cells communicate with the cells' interiors in the process that leads to the cells' collection of calcium.
1. Patel HH et al. Cholesterol-depleting drugs, including statins, lower intracellular Ca2+ and inhibit proliferation in pulmonary artery smooth muscle cells in primary pulmonary hypertension. 35th Congress of the International Union of Physiological Sciences. 2005 Mar 31-Apr 5. San Diego, CA.
2. Pulmonary Hypertension Association. What is PH? Available at: http://www.phassociation.org/Learn/What-is-PH/index.asp. Accessed April 14, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
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