Soluble guanylate cyclase allosteric modulators as anti-platelet therapy: in vitro, ex vivo and in vivo studies.

Author(s)

Plinio Minghin Freitas Ferreira

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2016-10-31

Examining board members

Gilberto de Nucci; Lucia Rossetti Lopes; Antonio de Padua Mansur; Marcelo Nicolas Muscara; José Carlos Nicolau

• Advisor: Gilberto de Nucci

Abstract

Disorders on the cardiovascular (CV) system are responsible for 31% of deaths worldwide. When inappropriately activated, platelets can cause myocardial infarction and stroke. Dual anti-platelet therapy (DAPT), composed of acetylsalicylic acid and a P2Y12 receptor blocker (clopidogrel, prasugrel, etc) is recommended for the prevention of recurrent CV events. Whilst DAPT is associated with an improvement in patient outcomes, thrombotic events do still occur. Platelet reactivity of patients under DAPT is a function of the level of P2Y12 receptor blockade and the levels of nitric oxide (NO) and prostacyclin (PGI2), two important endothelium-derived autacoids. Therefore, a new antithrombotic therapy is proposed using soluble guanylate cyclase (sGC) allosteric modulators independent of NO and phosphodiesterase (PDE) inhibitors. Based on the results observed, the combination of a sGC activator and a PDE inhibitor given at low doses, in the presence of P2Y12 receptor blocker, could produce enhanced and localized platelet inhibition. (AU)

• FAPESP's process: 13/04994-0 - Smooth muscle contraction mechanisms of Epicrates chencria and Boa constrictor
• Grantee: Plinio Minghin Freitas Ferreira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)