PM20D1 levels may predict mortality risk in idiopathic PAH
Studies needed to explore enzyme's regulatory mechanisms, lipid metabolism
Low levels of PM20D1, a molecule involved in metabolizing lipids, were identified as a risk factor for mortality in people with pulmonary arterial hypertension (PAH), a study reports.
As a result, PM20D1, or peptidase M20 domain containing 1, may be a biomarker of disease prognosis, according to scientists. Lipid metabolism is a complex process that includes the production, intake, degradation or conversion of fatty molecules.
“The findings from this study could elucidate the clinical relevance of PM20D1 in IPAH [idiopathic PAH] patients, and also present novel avenues for future research in IPAH treatment,” the researchers wrote in “Serum PM20D1 levels in patients with idiopathic pulmonary arterial hypertension and its clinical significance,” which was published in BMC Cardiovascular Disorders.
In PAH, the pulmonary arteries, or small blood vessels that transport blood through the lungs, narrow, which restricts blood flow through the lungs, causing high blood pressure and leading to right heart failure. In idiopathic PAH, the cause of the disease can’t be identified.
Studies have suggested an association between right heart dysfunction in PAH and abnormalities in lipid metabolism. Particularly, abnormal levels of the PM20D1 enzyme have been found in patients, said researchers.
“However, currently, there are no clinical studies investigating the relationship between PM20D1 and lipid metabolism factors in IPAH patients, as well as its impact on patient prognosis,” wrote researchers in China, who studied 103 adults (62% men) with idiopathic PAH who were followed for 540 days, or about 1.5 years. Almost a third (31) died during follow-up.
Mortality risk in lower levels of PM20D1
The patients who died were older (52.9 vs. 47) and had higher mean pulmonary arterial pressure, pulmonary vascular resistance, which is resistance to blood flow, and pulmonary capillary wedge pressure, an indicator of the pressure during left ventricle filling, over those who survived.
They also had a larger right atrium of the heart as well as less distance walked in six minutes (230.7 vs. 334 meters), a standard assessment of exercise capacity.
The investigators then assessed blood biomarker activity in the two groups and in 100 healthy volunteers, who served as controls. Compared with the controls, IPAH patients had significantly lower blood levels of PM20D1, low density lipoprotein cholesterol, which is dubbed “bad cholesterol,” and albumin, the most abundant protein in the bloodstream.
“These results suggested that PM20D1 might be linked to clinical outcomes in IPAH patients,” the researchers wrote.
Compared with the survival group, the patients who died had lower PM20D1 and albumin. Higher PM20D1 levels were associated with greater distance walked in six minutes and right ventricle function, as assessed by a measure called tricuspid annular plane systolic excursion, an analysis showed.
Further evaluation established a cutoff PM20D1 value of 4.48 ng/ml, below which patients had more risk of a worse prognosis. The sensitivity was 76.4%, and specificity was 74.2%. Sensitivity refers to a test’s ability to correctly identify patients with a certain condition, whereas specificity is the ability to correctly detect those who don’t have the condition.
In a subsequent, more complex analysis, both PM20D1 and albumin levels were identified as risk factors for mortality with IPAH. Other risk factors included pulmonary vascular resistance, the distance walked in six minutes, and a biomarker of heart health known as NT-proBNP.
“We identified [blood] serum PM20D1 as a potential predictor of survival in IPAH patients. This finding suggested that PM20D1 might play a crucial role in the [disease mechanisms] of IPAH and could serve as a potential prognostic marker,” wrote the researchers, who said studies “should explore the regulatory mechanisms of PM20D1 and its role in lipid metabolism in IPAH” and investigate if targeting the enzyme to treat IPAH has any therapeutic potential.
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