Academic Journal
ENDOTHELIUM-SPECIFIC DEFICIENCY OF POLYCYSTIN-1 PROMOTES HYPERTENSION AND CARDIOVASCULAR DISORDERS
| Title: | ENDOTHELIUM-SPECIFIC DEFICIENCY OF POLYCYSTIN-1 PROMOTES HYPERTENSION AND CARDIOVASCULAR DISORDERS |
|---|---|
| Authors: | Guerrot, Dominique, Hamzaoui, Mouad, Groussard, Deborah, Nezam, Dorian, Mulder, Paul, Richard, Vincent, Bellien, Jeremy |
| Source: | Journal of Hypertension ; volume 40, issue Suppl 1, page e38 ; ISSN 0263-6352 1473-5598 |
| Publisher Information: | Ovid Technologies (Wolters Kluwer Health) |
| Publication Year: | 2022 |
| Description: | Objective: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary kidney disease and is generally due to mutations in PKD1 and PKD2, encoding polycystins 1 and 2. In ADPKD, hypertension and cardiovascular (CV) disorders are highly prevalent but their mechanisms are partially understood. The objective of this study was to determine whether hypertension and the CV disorders of ADPKD are a consequence of the endothelial deficiency in the polycystin complex, rather than to the kidney disease, as is currently believed. Design and method: Since endothelial cells express the polycystin complex, where it plays a central role in the mechanotransduction of blood flow, we generated a murine model with inducible deletion of Pkd1 in endothelial cells (Cdh5-CreERT2;Pkd1fl/fl) to specifically determine the role of endothelial polycystin-1 in ADPKD. We nalysed the endothelial phenotype associated with Pkd1 deficiency, invasive and non-invasive blood pressure, vascular function on isolated vessels, and echocardiography. The impact on the development of a model of aorto-cava arterio-venous fistula and on the CV consequences of superimposed chronic kidney disease were nalysed to further establish the clinical relevance of our results. Results: As expected, transgenic mice presented normal kidney structure and function. Endothelial deletion of Pkd1 induced endothelial dysfunction, as demonstrated by impaired flow-mediated dilatation of resistance arteries and impaired relaxation to acetylcholine, increased blood pressure and prevented the normal development of arterio-venous fistula. In experimental chronic kidney disease induced by subtotal nephrectomy, endothelial deletion of Pkd1 further aggravated endothelial dysfunction, vascular remodelling and heart hypertrophy. Conclusions: Altogether, this study provides the first in vivo demonstration that specific deletion of Pkd1 in endothelial cells promotes endothelial dysfunction and hypertension independently of kidney cysts and of impaired kidney ... |
| Document Type: | article in journal/newspaper |
| Language: | English |
| DOI: | 10.1097/01.hjh.0000835596.33668.f9 |
| Availability: | https://doi.org/10.1097/01.hjh.0000835596.33668.f9 https://journals.lww.com/10.1097/01.hjh.0000835596.33668.f9 |
| Accession Number: | edsbas.641FCD76 |
| Database: | BASE |
| FullText | Text: Availability: 0 CustomLinks: – Url: https://doi.org/10.1097/01.hjh.0000835596.33668.f9# Name: EDS - BASE (ns324271) Category: fullText Text: View record from BASE |
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| Items | – Name: Title Label: Title Group: Ti Data: ENDOTHELIUM-SPECIFIC DEFICIENCY OF POLYCYSTIN-1 PROMOTES HYPERTENSION AND CARDIOVASCULAR DISORDERS – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Guerrot%2C+Dominique%22">Guerrot, Dominique</searchLink><br /><searchLink fieldCode="AR" term="%22Hamzaoui%2C+Mouad%22">Hamzaoui, Mouad</searchLink><br /><searchLink fieldCode="AR" term="%22Groussard%2C+Deborah%22">Groussard, Deborah</searchLink><br /><searchLink fieldCode="AR" term="%22Nezam%2C+Dorian%22">Nezam, Dorian</searchLink><br /><searchLink fieldCode="AR" term="%22Mulder%2C+Paul%22">Mulder, Paul</searchLink><br /><searchLink fieldCode="AR" term="%22Richard%2C+Vincent%22">Richard, Vincent</searchLink><br /><searchLink fieldCode="AR" term="%22Bellien%2C+Jeremy%22">Bellien, Jeremy</searchLink> – Name: TitleSource Label: Source Group: Src Data: Journal of Hypertension ; volume 40, issue Suppl 1, page e38 ; ISSN 0263-6352 1473-5598 – Name: Publisher Label: Publisher Information Group: PubInfo Data: Ovid Technologies (Wolters Kluwer Health) – Name: DatePubCY Label: Publication Year Group: Date Data: 2022 – Name: Abstract Label: Description Group: Ab Data: Objective: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary kidney disease and is generally due to mutations in PKD1 and PKD2, encoding polycystins 1 and 2. In ADPKD, hypertension and cardiovascular (CV) disorders are highly prevalent but their mechanisms are partially understood. The objective of this study was to determine whether hypertension and the CV disorders of ADPKD are a consequence of the endothelial deficiency in the polycystin complex, rather than to the kidney disease, as is currently believed. Design and method: Since endothelial cells express the polycystin complex, where it plays a central role in the mechanotransduction of blood flow, we generated a murine model with inducible deletion of Pkd1 in endothelial cells (Cdh5-CreERT2;Pkd1fl/fl) to specifically determine the role of endothelial polycystin-1 in ADPKD. We nalysed the endothelial phenotype associated with Pkd1 deficiency, invasive and non-invasive blood pressure, vascular function on isolated vessels, and echocardiography. The impact on the development of a model of aorto-cava arterio-venous fistula and on the CV consequences of superimposed chronic kidney disease were nalysed to further establish the clinical relevance of our results. Results: As expected, transgenic mice presented normal kidney structure and function. Endothelial deletion of Pkd1 induced endothelial dysfunction, as demonstrated by impaired flow-mediated dilatation of resistance arteries and impaired relaxation to acetylcholine, increased blood pressure and prevented the normal development of arterio-venous fistula. In experimental chronic kidney disease induced by subtotal nephrectomy, endothelial deletion of Pkd1 further aggravated endothelial dysfunction, vascular remodelling and heart hypertrophy. Conclusions: Altogether, this study provides the first in vivo demonstration that specific deletion of Pkd1 in endothelial cells promotes endothelial dysfunction and hypertension independently of kidney cysts and of impaired kidney ... – Name: TypeDocument Label: Document Type Group: TypDoc Data: article in journal/newspaper – Name: Language Label: Language Group: Lang Data: English – Name: DOI Label: DOI Group: ID Data: 10.1097/01.hjh.0000835596.33668.f9 – Name: URL Label: Availability Group: URL Data: https://doi.org/10.1097/01.hjh.0000835596.33668.f9<br />https://journals.lww.com/10.1097/01.hjh.0000835596.33668.f9 – Name: AN Label: Accession Number Group: ID Data: edsbas.641FCD76 |
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