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

Author(s)

Miotto, Danyelle S. ^{[1, 2]} ; Dionizio, Aline ^[3] ; Jacomini, Andre M. ^[4] ; Zago, Anderson S. ^{[5, 4]} ; Buzalaf, Marilia Afonso Rabelo ^[3] ; Amaral, Sandra L. ^{[1, 2, 5]}

Affiliation

^[1] Univ Fed Sao Carlos, Joint Grad Program Physiol Sci, Sao Carlos - Brazil

^[2] Sao Paulo State Univ, UFSCar UNESP, Sao Carlos - Brazil

^[3] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, Bauru, SP - Brazil

^[4] Sao Paulo State Univ, Postgrad Program Movement Sci, Bauru, SP - Brazil

^[5] Sao Paulo State Univ, Sch Sci, Dept Phys Educ, Bauru, SP - Brazil

• Document type: Journal article
• Source: FRONTIERS IN PHYSIOLOGY; v. 12, FEB 10 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 17/00509-1 - Role of physical training on autonomic balance, arterial stiffness and rarefaction in spontaneously hypertensive rats treated with dexamethasone: role of miRNA
• Grantee: Sandra Lia do Amaral Cardoso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/12041-7 - Safety and efficacy for the prevention of dental erosion of a new cystatin derived from sugarcane (CaneCPI-5): in vitro, in situ and in vivo studies
• Grantee: Marília Afonso Rabelo Buzalaf
• Support Opportunities: Regular Research Grants