Regulatory mechanisms in pulmonary blood vessels - new "player" identified

News 2022-074 EN

Pulmonary hypertension (PH) is a life-threatening disease characterized by massive remodeling of the pulmonary vessels from delicate-walled capillaries to thick-walled narrow vessels. This massively restricts gas exchange and places a strain on the right heart. Despite much progress - including by DZL scientists and clinicians - PH is still not curable.

In order to understand the molecular causes of these remodeling processes and thus open up new therapeutic options, both tissue samples from patients and experimental models were used in the study by Veith et al. One of the factors identified in these approaches is the so-called SPARC protein (protein acidic and rich in cysteine). Both in the hypoxia-induced experimental PH model and in lung tissue from patients, SPARC was upregulated in a tissue-specific manner. Induction of SPARC by hypoxia or hypoxia mediators (such as HIF-hypoxia-inducible factor) increased proliferation and decreased apoptosis in pulmonary arterial muscle cells (PASMC); addition/increase of SPARC had the opposite effect. In co-cultures of PASMC and pulmonary vascular endothelial cells (PMVEC), SPARC was shown to be secreted by PMVEC and to induce proliferation of PASMC. In the experimental model, a "knock-down" of SPARC was able to improve hemodynamics.

The identification of this new "player" in the regulation of pulmonary vascular pressure is another piece in the "puzzle" of aberrant vascular regulation in PH.


Further information:

Veith C, Vartürk-Özcan I, Wujak M, Hadzic S, Wu CY, Knoepp F, Kraut S, Petrovic A, Gredic M, Pak O, Brosien M, Heimbrodt M, Wilhelm J, Weisel FC, Malkmus K, Schäfer K, Gall H, Tello K, Kosanovic D, Sydykov A, Sarybaev A, Günther A, Brandes RP, Seeger W, Grimminger F, Ghofrani HA, Schermuly RT, Kwapiszewska G, Sommer N, Weissmann N. SPARC, a Novel Regulator of Vascular Cell Function in Pulmonary Hypertension. Circulation. 2022 Mar 22;145(12):916-933. doi: 10.1161/CIRCULATIONAHA.121.057001. Epub 2022 Feb 17. PMID: 35175782.

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