A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”

Abstract Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Many CVDs begin with endothelium dysfunction (ED), including hypertension, thrombosis, and atherosclerosis. Our assay evaluated ED in isolated murine aorta by quantifying phenylephrine‐induced contractio...

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Autores principales:	Lexiao Jin, Daniel J. Conklin
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	aldehydes cardiovascular disease endothelium eNOS L‐NAME Physiology QP1-981
Acceso en línea:	https://doaj.org/article/8ded912e18ec4bbda00c73a3f8163c8f
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spelling	oai:doaj.org-article:8ded912e18ec4bbda00c73a3f8163c8f2021-11-15T09:54:41ZA novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”2051-817X10.14814/phy2.15120https://doaj.org/article/8ded912e18ec4bbda00c73a3f8163c8f2021-11-01T00:00:00Zhttps://doi.org/10.14814/phy2.15120https://doaj.org/toc/2051-817XAbstract Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Many CVDs begin with endothelium dysfunction (ED), including hypertension, thrombosis, and atherosclerosis. Our assay evaluated ED in isolated murine aorta by quantifying phenylephrine‐induced contractions (PE) in the presence of L‐NAME, which blocked acetylcholine‐induced relaxation (ACh %; >99%). The “L‐NAME PE Contraction Ratio” (PECR) was defined as: “PE Tension post‐L‐NAME” divided by “PE Tension pre‐L‐NAME.” We hypothesized that our novel PE Contraction Ratio would strongly correlate with alterations in endothelium function. Validation 1: PECR and ACh % values of naïve aortas were strongly and positively correlated (PECR vs. ACh %, r2 = 0.91, n = 7). Validation 2: Retrospective analyses of published aortic PECR and ACh % data of female mice exposed to filtered air, propylene glycol:vegetable glycerin (PG:VG), formaldehyde (FA), or acetaldehyde (AA) for 4d showed that the PECR in air‐exposed mice (PECR = 1.43 ± 0.05, n = 16) correlated positively with the ACh % (r2 = 0.40) as seen in naïve aortas. Similarly, PECR values were significantly decreased in aortas with ED yet retained positive regression coefficients with ACh % (PG:VG r2 = 0.54; FA r2 = 0.55). Unlike other toxicants, inhaled AA significantly increased both PECR and ACh % values yet diminished their correlation (r2 = 0.09). Validation 3: To assess species‐specific dependence, we tested PECR in rat aorta, and found PECR correlated with ACh % relaxation albeit less well in this aged and dyslipidemic model. Because the PECR reflects NOS function directly, it is a robust measure of both ED and vascular dysfunction. Therefore, it is a complementary index of existing tests of ED that also provides insight into mechanisms of vascular toxicity.Lexiao JinDaniel J. ConklinWileyarticlealdehydescardiovascular diseaseendotheliumeNOSL‐NAMEPhysiologyQP1-981ENPhysiological Reports, Vol 9, Iss 21, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aldehydes cardiovascular disease endothelium eNOS L‐NAME Physiology QP1-981
spellingShingle	aldehydes cardiovascular disease endothelium eNOS L‐NAME Physiology QP1-981 Lexiao Jin Daniel J. Conklin A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”
description	Abstract Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Many CVDs begin with endothelium dysfunction (ED), including hypertension, thrombosis, and atherosclerosis. Our assay evaluated ED in isolated murine aorta by quantifying phenylephrine‐induced contractions (PE) in the presence of L‐NAME, which blocked acetylcholine‐induced relaxation (ACh %; >99%). The “L‐NAME PE Contraction Ratio” (PECR) was defined as: “PE Tension post‐L‐NAME” divided by “PE Tension pre‐L‐NAME.” We hypothesized that our novel PE Contraction Ratio would strongly correlate with alterations in endothelium function. Validation 1: PECR and ACh % values of naïve aortas were strongly and positively correlated (PECR vs. ACh %, r2 = 0.91, n = 7). Validation 2: Retrospective analyses of published aortic PECR and ACh % data of female mice exposed to filtered air, propylene glycol:vegetable glycerin (PG:VG), formaldehyde (FA), or acetaldehyde (AA) for 4d showed that the PECR in air‐exposed mice (PECR = 1.43 ± 0.05, n = 16) correlated positively with the ACh % (r2 = 0.40) as seen in naïve aortas. Similarly, PECR values were significantly decreased in aortas with ED yet retained positive regression coefficients with ACh % (PG:VG r2 = 0.54; FA r2 = 0.55). Unlike other toxicants, inhaled AA significantly increased both PECR and ACh % values yet diminished their correlation (r2 = 0.09). Validation 3: To assess species‐specific dependence, we tested PECR in rat aorta, and found PECR correlated with ACh % relaxation albeit less well in this aged and dyslipidemic model. Because the PECR reflects NOS function directly, it is a robust measure of both ED and vascular dysfunction. Therefore, it is a complementary index of existing tests of ED that also provides insight into mechanisms of vascular toxicity.
format	article
author	Lexiao Jin Daniel J. Conklin
author_facet	Lexiao Jin Daniel J. Conklin
author_sort	Lexiao Jin
title	A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”
title_short	A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”
title_full	A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”
title_fullStr	A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”
title_full_unstemmed	A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”
title_sort	novel evaluation of endothelial dysfunction ex vivo: “teaching an old drug a new trick”
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/8ded912e18ec4bbda00c73a3f8163c8f
work_keys_str_mv	AT lexiaojin anovelevaluationofendothelialdysfunctionexvivoteachinganolddruganewtrick AT danieljconklin anovelevaluationofendothelialdysfunctionexvivoteachinganolddruganewtrick AT lexiaojin novelevaluationofendothelialdysfunctionexvivoteachinganolddruganewtrick AT danieljconklin novelevaluationofendothelialdysfunctionexvivoteachinganolddruganewtrick
_version_	1718428446168711168

A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”

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