Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension?

Abstract

Cardiovascular diseases (CVD) are the leading cause of premature death and disability in humans that are closely related to lipid metabolism and signaling. This study aimed to assess whether circulating lysophospholipids (LPL), lysophosphatidic acids (LPA) and monoacylglycerols (MAG) may be considered as potential therapeutic targets in CVD. For this objective, plasma levels of 22 compounds (13 LPL, 6 LPA and 3 MAG) were monitored by liquid chromatography coupled with tandem mass spectrometry (HPLC/MS2) in different rat models of CVD, i.e., angiotensin-II-induced hypertension (HTN), ischemic chronic heart failure (CHF) and sugen/hypoxia(SuHx)-induced pulmonary hypertension (PH). On one hand, there were modest changes on the monitored compounds in HTN (LPA 16:0, 18:1 and 20:4, LPC 16:1) and CHF (LPA 16:0, LPC 18:1 and LPE 16:0 and 18:0) models compared to control rats but these changes were no longer significant after multiple testing corrections. On the other hand, PH was associated with important changes in plasma LPA with a significant increase in LPA 16:0, 18:1, 18:2, 20:4 and 22:6 species. A deleterious impact of LPA was confirmed on cultured human pulmonary smooth muscle cells (PA-SMCs) with an increase in their proliferation. Finally, plasma level of LPA(16:0) was positively associated with the increase in pulmonary artery systolic pressure in patients with cardiac dysfunction. This study demonstrates that circulating LPA may contribute to the pathophysiology of PH. Additional experiments are needed to assess whether the modulation of LPA signaling in PH may be of interest.

The Impact of Abnormal Lipid Metabolism on the Occurrence Risk of Idiopathic Pulmonary Arterial Hypertension

“…This study found that MAG was an independent risk factor for IPAH. This is consistent with previous research indicating that MAG plays a significant role in cardiovascular disease and may serve as a potential therapeutic target [ 28 ], but its role in IPAH was unknown. Our results showed that MAG might be of significance in the development of IPAH.…”

Identification of urine biomarkers predictive of prolonged QTc interval in multidrug-resistant tuberculosis patients treated with bedaquiline

“…Taken together, the elevated level of LPEs may reflect high susceptibility to heart diseases. In line with our hypothesis, an experimental study by Duflot and colleagues found that circulating LPE species were increased in rats with cardiovascular disease, suggesting their role in the pathophysiology of this disease ( Duflot et al, 2021 ). Further studies are warranted to elucidate the underlying molecular mechanisms of LPEs in predicting cardiovascular adverse events.…”