Identification of Aortic Proteins Involved in Arterial Stiffness in Spontaneously Hypertensive Rats Treated With Perindopril:A Proteomic Approach

Abstract

Arterial stiffness, frequently associated with hypertension, is associated with disorganization of the vascular wall and has been recognized as an independent predictor of all-cause mortality. The identification of the molecular mechanisms involved in aortic stiffness would be an emerging target for hypertension therapeutic intervention. This study evaluated the effects of perindopril on pulse wave velocity (PWV) and on the differentially expressed proteins in aorta of spontaneously hypertensive rats (SHR), using a proteomic approach. SHR and Wistar rats were treated with perindopril (SHRP) or water (SHRc and Wistar rats) for 8 weeks. At the end, SHRC presented higher systolic blood pressure (SBP, +70%) and PWV (+31%) compared with Wistar rats. SHRP had higher values of nitrite concentration and lower PWV compared with SHRC. From 21 upregulated proteins in the aortic wall from SHRC, most of them were involved with the actin cytoskeleton organization, like Tropomyosin and Cofilin-1. After perindopril treatment, there was an upregulation of the GDP dissociation inhibitors (GDIs), which normally inhibits the RhoA/Rho-kinase/cofilin-1 pathway and may contribute to decreased arterial stiffening. In conclusion, the results of the present study revealed that treatment with perindopril reduced SBP and PWV in SHR. In addition, the proteomic analysis in aorta suggested, for the first time, that the RhoA/Rho-kinase/Cofilin-1 pathway may be inhibited by perindopril-induced upregulation of GDIs or increases in NO bioavailability in SHR. Therefore, we may propose that activation of GDIs or inhibition of RhoA/Rho-kinase pathway could be a possible strategy to treat arterial stiffness.

Genetic Factors for Coronary Heart Disease and Their Mechanisms: A Meta-Analysis and Comprehensive Review of Common Variants from Genome-Wide Association Studies

“…Previous works have reported that PECAM-1 is an important feature of differentiated VSMCs [ 103 ], whereas the hypercontractility phenotype of differentiated VSMCs usually seen in diabetes and hypertension was correlated with RhoA upregulation [ 104 ]. Moreover, spontaneously hypertensive rats did not suffer increased arterial stiffness alone [ 105 ]. Additionally, proteomics analysis of their aortic tissues revealed higher expression of RhoA, along with other proteins involved in the actin cytoskeleton organization [ 105 ], indicating that arterial stiffness, as well as hypertension, were dependent on a similar mechanism governing cellular stiffening.…”

Benefits of combined exercise training on arterial stiffness and blood pressure in spontaneously hypertensive rats treated or not with dexamethasone

“…At the beginning and on the 12th day of the experimental protocol ( Figure 1 ), PWV assessments were performed following the procedures already published by our group ( Fabricio et al, 2020 ; Miotto et al, 2021a ; Tardelli et al, 2021 ). In summary, the two pOpet ® probes (Axelife SAS, Saint Nicolas de Redon, France) were positioned on the right forelimb and hindlimb of the anesthetized rats.…”

“…All animals were adapted for 5 days to the cylindrical acrylic tube that kept the rats at rest and, during the 8-weeks period of combined training, systolic blood pressure assessments were performed at the beginning, after 30 and 60 days, as stated in Figure 1 , following the procedures already published ( Miotto et al, 2021a ; Miotto et al, 2021b ). A cuff was positioned around the tail of the animals and systolic blood pressure (SBP) was recorded by tail-cuff plethysmography system (PanLab LE5001, Barcelona, Spain).…”

“…As shown in Figure 1 , on the 14th day of the treatment with DEX, all rats were anesthetized and the carotid artery was catheterized for direct BP measurements following the procedures previously described by our laboratory ( Herrera et al, 2016 ; Constantino et al, 2017 ; Herrera et al, 2017 ; Duchatsch et al, 2018 ; Jesus et al, 2020 ; Miotto et al, 2021a ; Miotto et al, 2021b ; Duchatsch et al, 2021 ; Tardelli et al, 2021 ). On the next day, BP was recorded in conscious freely moving rats using a Software LabChart Pro 7.1 (ADInstruments, NSW, Australia).…”

Microgravity × Radiation: A Space Mechanobiology Approach Toward Cardiovascular Function and Disease

“…Arterial stiffness has also been believed to be a precursor to atherosclerosis and a marker for increased cardiovascular disease risk such as myocardial infarction (O'Rourke, 1995;Safar et al, 2003;Zieman et al, 2005). The majority of upregulated proteins in the aortic wall are involved in the actin cytoskeleton organization and by identifying the exact molecular mechanism and mechanical regulators associated with arterial stiffness, it can aid in identifying therapeutic intervention (Miotto et al, 2021). Interestingly, the increased stiffness in the carotid artery that is normally seen in the aging cardiovascular system in the population can be simulated by spaceflight (Kawasaki et al, 1987;Lakatta and Levy, 2003;Gepner et al, 2014;Hughson et al, 2016).…”