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1.	Schwartz, GG, et al. (author) Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome 2018 In: The New England journal of medicine. - : MASSACHUSETTS MEDICAL SOC. - 1533-4406 .- 0028-4793. ; 379:22, s. 2097-2107 Journal article (peer-reviewed)
2.	Cat, Aurelie Nguyen Dinh, et al. (author) Vascular dysfunction in obese diabetic db/db mice involves the interplay between aldosterone/mineralocorticoid receptor and Rho kinase signaling 2018 In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8 Journal article (peer-reviewed)abstract Activation of aldosterone/mineralocorticoid receptors (MR) has been implicated in vascular dysfunction of diabetes. Underlying mechanisms are elusive. Therefore, we investigated the role of Rho kinase (ROCK) in aldosterone/MR signaling and vascular dysfunction in a model of diabetes. Diabetic obese mice (db/db) and control counterparts (db/+) were treated with MR antagonist (MRA, potassium canrenoate, 30 mg/kg/day, 4 weeks) or ROCK inhibitor, fasudil (30 mg/kg/day, 3 weeks). Plasma aldosterone was increased in db/db versus db/+. This was associated with enhanced vascular MR signaling. Norepinephrine (NE)-induced contraction was increased in arteries from db/db mice. These responses were attenuated in mice treated with canrenoate or fasudil. Db/db mice displayed hypertrophic remodeling and increased arterial stiffness, improved by MR blockade. Vascular calcium sensitivity was similar between depolarized arteries from db/+ and db/db. Vascular hypercontractility in db/db mice was associated with increased myosin light chain phosphorylation and reduced expression of PKG-1 alpha. Vascular RhoA/ROCK signaling and expression of pro-inflammatory and pro-fibrotic markers were exaggerated in db/db mice, effects that were attenuated by MRA. Fasudil, but not MRA, improved vascular insulin sensitivity in db/db mice, evidenced by normalization of Irs1 phosphorylation. Our data identify novel pathways involving MR-RhoA/ROCK-PKG-1 that underlie vascular dysfunction and injury in diabetic mice.

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Type of publication: journal article (2)

Type of content: peer-reviewed (2)

Author/Editor: King, M. (1); Li, Y. (1); Schmidt, E. (1); Zaman, A. (1); Zhang, Z. (1); Zhu, H. (1); show more...; Guo, Y (1); Ahmed, H. (1); Kaiser, S. (1); Nikolaev, K. (1); Schwartz, M. (1); Kumar, A. (1); Robinson, S. (1); Zheng, Y. (1); Costa, F. (1); Das, S. (1); Diaz, R. (1); Mahajan, A. (1); Davies, R (1); Aggarwal, R. (1); Andersen, K (1); Diaz, A. (1); Cohen, S. (1); Rosenberg, M. (1); Gullestad, L (1); Hong, T. (1); Kumar, P. (1); Khan, A. (1); Davis, W. (1); Aboyans, V (1); Khan, M (1); Liu, SW (1); Pandey, A (1); Sarkar, D. (1); Hoffman, D (1); Takahashi, T. (1); Marx, R. (1); Bottcher, M. (1); White, M. (1); Seferovic, P (1); Wells, T (1); Katz, A. (1); Ito, K. (1); Kobayashi-, J (1); Harding, S (1); Huang, L. (1); Anderson, J (1); Vulic, D (1); Pearce, S (1); Gerber, J. (1); show less...

University: Uppsala University (2); Karolinska Institutet (1)

Language: English (2)

Research subject (UKÄ/SCB): Medical and Health Sciences (2)

Year: 2018 (2)Undo refine

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