Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension?
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 consider...
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2021
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oai:doaj.org-article:2813d9874b6f4b77aef908b7dc9296a52021-11-25T18:20:54ZPreventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension?10.3390/metabo111107842218-1989https://doaj.org/article/2813d9874b6f4b77aef908b7dc9296a52021-11-01T00:00:00Zhttps://www.mdpi.com/2218-1989/11/11/784https://doaj.org/toc/2218-1989Cardiovascular 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/MS<sup>2</sup>) 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.Thomas DuflotLy TuMatthieu LeuillierHind MessaoudiDéborah GroussardGuillaume FeugraySaïda AzharRaphaël ThuilletFabrice BauerMarc HumbertVincent RichardChristophe GuignabertJérémy BellienMDPI AGarticlelysophospholipidslysophosphatidic acidscardiovascular diseasesHPLC-MS/MSrodent modelspulmonary hypertensionMicrobiologyQR1-502ENMetabolites, Vol 11, Iss 784, p 784 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
lysophospholipids lysophosphatidic acids cardiovascular diseases HPLC-MS/MS rodent models pulmonary hypertension Microbiology QR1-502 |
| spellingShingle |
lysophospholipids lysophosphatidic acids cardiovascular diseases HPLC-MS/MS rodent models pulmonary hypertension Microbiology QR1-502 Thomas Duflot Ly Tu Matthieu Leuillier Hind Messaoudi Déborah Groussard Guillaume Feugray Saïda Azhar Raphaël Thuillet Fabrice Bauer Marc Humbert Vincent Richard Christophe Guignabert Jérémy Bellien Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension? |
| description |
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/MS<sup>2</sup>) 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. |
| format |
article |
| author |
Thomas Duflot Ly Tu Matthieu Leuillier Hind Messaoudi Déborah Groussard Guillaume Feugray Saïda Azhar Raphaël Thuillet Fabrice Bauer Marc Humbert Vincent Richard Christophe Guignabert Jérémy Bellien |
| author_facet |
Thomas Duflot Ly Tu Matthieu Leuillier Hind Messaoudi Déborah Groussard Guillaume Feugray Saïda Azhar Raphaël Thuillet Fabrice Bauer Marc Humbert Vincent Richard Christophe Guignabert Jérémy Bellien |
| author_sort |
Thomas Duflot |
| title |
Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension? |
| title_short |
Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension? |
| title_full |
Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension? |
| title_fullStr |
Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension? |
| title_full_unstemmed |
Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension? |
| title_sort |
preventing the increase in lysophosphatidic acids: a new therapeutic target in pulmonary hypertension? |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/2813d9874b6f4b77aef908b7dc9296a5 |
| work_keys_str_mv |
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