Matrix Metalloproteinase-2 Proteolyzes the Sarcoplasmic Reticulum Calcium ATPase (SERCA), thus Resulting in Morphofunctional Vascular Alterations in Arterial Hypertension

Autor: Marcela Blascke de Mello, Viviano Gomes de Oliveira Neves, Laena Pernomian, Juliana Montenegro Parente, Eduardo Vieira da Rocha, Michele Mazzaron de Castro
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
DOI: 10.1152/physiol.2023.38.s1.5731655
Popis: Introduction: Arterial hypertension is characterized by matrix metalloproteinase (MMP)-2 increased activity, which proteolyzes extra- and intracellular proteins, thus contributing to cellular migration and proliferation and resulting in vascular remodeling and dysfunction. MMP-2 also proteolyzes the sarcoplasmic reticulum calcium ATPase (SERCA) in myocardial ischemia and reperfusion injury, thus impairing cardiac contractile function. SERCA activity can be also reduced in the arteries of hypertensive animals. The hypothesis is hypertension-induced increased MMP-2 activity contributes to proteolyze aortic SERCA, thus resulting in vascular remodeling and dysfunction. Method: Male Sprague-Dawley rats were submitted to two kidney-one clip (2K-1C) or Sham surgery and treated with water or doxycycline (Doxy, 30 mg/kg/day). Systolic blood pressure (SBP) was assessed basally and daily from 1st to 7th day post-surgery by tail-cuff plethysmography. Then, aortas were collected for gelatin and in situ zymography, western blot to SERCA, immunofluorescence to calcium and Ki-67, morphological analysis by hematoxilin and eosin stain, vascular reactivity to phenylephrine and acetylcholine and ATPase (SERCA) activity assay. Statistical analysis was done by two-way ANOVA followed by Tukey post-test. The Ethics Committee for Animal Research of the Ribeirao Preto Medical School approved all protocols (122/2019). Results: SBP increased in 2K-1C rats vs. Sham groups (n=9; p CAPES, CNPq and FAPESP This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Databáze: OpenAIRE