Universität zu Köln

Batool, Mehreen, Berghausen, Eva M., Zierden, Mario, Vantler, Marius, Schermuly, Ralph T., Baldus, Stephan, Rosenkranz, Stephan and ten Freyhaus, Henrik (2020). The six-transmembrane protein Stamp2 ameliorates pulmonary vascular remodeling and pulmonary hypertension in mice. Basic Res. Cardiol., 115 (6). HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1435-1803

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Abstract

Six-transmembrane protein of prostate (Stamp2) protects from diabetes and atherosclerosis in mice via anti-inflammatory mechanisms. As chronic inflammation is a hallmark of pulmonary arterial hypertension (PAH), we investigated the role of Stamp2. Stamp2 expression was substantially reduced in the lung of humans with idiopathic PAH, as well as in experimental PAH. In Stamp2-deficient mice, hypoxia modestly aggravated pulmonary vascular remodeling and right ventricular pressure compared to WT. As endothelial cell (EC) and pulmonary arterial smooth muscle cell (PASMC) phenotypes drive remodeling in PAH, we explored the role of Stamp2. Knock-down of Stamp2 in human EC neither affected apoptosis, viability, nor release of IL-6. Moreover, Stamp2 deficiency in primary PASMC did not alter mitogenic or migratory properties. As Stamp2 deficiency augmented expression of inflammatory cytokines and numbers of CD68-positive cells in the lung, actions of Stamp2 in macrophages may drive vascular remodeling. Thus, PASMC responses were assessed following treatment with conditioned media of primary Stamp2(-/-) or WT macrophages. Stamp2(-/-) supernatants induced PASMC proliferation and migration stronger compared to WT. A cytokine array revealed CXCL12, MCP-1 and IL-6 as most relevant candidates. Experiments with neutralizing antibodies confirmed the role of these cytokines in driving Stamp2's responses. In conclusion, Stamp2 deficiency aggravates pulmonary vascular remodeling via cross-talk between macrophages and PASMC. Despite a substantial pro-inflammatory response, the hemodynamic effect of Stamp2 deficiency is modest suggesting that additional mechanisms apart from inflammation are necessary to induce severe PAH.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Batool, Mehreen UNSPECIFIED UNSPECIFIED UNSPECIFIED Berghausen, Eva M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zierden, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Vantler, Marius UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermuly, Ralph T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baldus, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenkranz, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED ten Freyhaus, Henrik UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-311459
DOI:	10.1007/s00395-020-00826-8
Journal or Publication Title:	Basic Res. Cardiol.
Volume:	115
Number:	6
Date:	2020
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1435-1803
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PATHOGENESIS; MIGRATION; PROMOTES; MOUSE; STEAP Multiple languages Cardiac & Cardiovascular Systems Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31145