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Potential Therapy Targets for Pulmonary Hypertension ID'd

In rodent models, apolipoprotein A-I mimetic peptide acts by inducing miR193 expression

Potential Therapy Targets for Pulmonary Hypertension ID'd

THURSDAY, Sept. 4, 2014 (HealthDay News) -- The high-density lipoprotein mimetic peptide 4F can successfully rescue advanced pulmonary hypertension in rodent models, according to a study published in Circulation.

Salil Sharma, Ph.D., from the University of California, Los Angeles, and colleagues studied two rodent models of pulmonary hypertension -- a monocrotaline rat model and a hypoxia mouse model -- to understand the role of oxidized lipids in the progression of pulmonary arterial hypertension.

The researchers found that plasma levels of hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids were significantly elevated in pulmonary hypertension. Treatment with 4F cut these levels and rescued pre-existing pulmonary hypertension in both models. MicroRNA-193-3p (miR193) was significantly downregulated in the serum and lung tissue from patients with pulmonary arterial hypertension and rodents with pulmonary hypertension. Pre-existing pulmonary hypertension was rescued with in vivo miR193 overexpression in the lungs, resulting in downregulation of lipoxygenases and insulin-like growth factor-1 receptor.

"These studies establish the importance of microRNAs as downstream effectors of an apolipoprotein A-I mimetic peptide in the rescue of pulmonary hypertension and suggest that treatment with apolipoprotein A-I mimetic peptides or miR193 may have therapeutic value," the authors write.

Several authors report financial ties to the pharmaceutical industry.

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