A protein in "good" cholesterol may help treat pulmonary hypertension, a serious lung disease that narrows the small blood vessels in the lungs, researchers, including one of Indian-origin, have found. A new study at University of California, Los Angeles (UCLA) demonstrates that oxidised lipids may contribute to pulmonary hypertension. Using a rodent model, researchers showed that a peptide mimicking part of the main protein in high-density lipoprotein (HDL), the so-called "good" cholesterol, may help reduce the production of oxidised lipids in pulmonary hypertension. They also found that reducing the amount of oxidised lipids improved the rodents' heart and lung function. A rare progressive condition, pulmonary hypertension can affect people of all ages.
The disease makes it harder for the heart to pump blood through these vital organs, which can lead to heart failure. "Our research helps unravel the mechanisms involved in the development of pulmonary hypertension," said Dr Mansoureh Eghbali, the study's senior author and an associate professor of anaesthesiology at David Geffen School of Medicine at UCLA. "A key peptide related to HDL cholesterol that can help reduce these oxidised lipids may provide a new target for treatment development," said Eghbali. Lipids such as fatty acids become oxidised when they are exposed to free radicals - tiny particles that are produced when the body converts food into energy - or when they are exposed to pollution, and in numerous other ways. Although researchers have known that oxidised lipids played a role in the development of atherosclerosis and other vascular diseases, the team discovered higher-than-normal levels of oxidised proteins in rodents with pulmonary hypertension. The researchers also knew that apoA-1, a protein that is a key component of HDL cholesterol, can reduce oxidised lipids, so they used a small peptide called 4F that mimics the action of apoA-1 and found that the 4F not only decreased the levels of oxidised lipids in the rodents, but also improved their heart and lung function. Specifically, the peptide restored the altered expression of a key molecule called micro ribonucleic acid (microRNA-193), which targets the action of essential enzymes involved in the production of oxidised lipids. "The increased amounts of these oxidised lipids due to pulmonary hypertension keeps the expression of this molecule under check, which aggravates symptoms of the disease," said first author Dr Salil Sharma, a UCLA postdoctoral researcher in anaesthesiology. By restoring the expression of microRNA-193 to its full potential, the researchers reduced the amount of oxidised lipids in the animals with pulmonary hypertension. The study appears in the journal Circulation.