Study of vascular responsiveness as a consequence of Cardiorenal Syndrome: participation of purinergic system

• Grant number: 19/12219-3
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: February 29, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Cristina Ribas Fürstenau
• Grantee: Cristina Ribas Fürstenau
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Santo André , SP, Brazil
• Associated researchers: Marcela Sorelli Carneiro Ramos

Abstract

Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide, representing around 31% of all global deaths. The heart is responsible for ensuring that blood circulates throughout the body, including the kidneys. The kidneys are responsible for filtering circulating blood, managing electrolyte homeostasis. Thus, the maintenance of cardiovascular homeostasis depends on fine interactions between the heart and kidneys. The existence of double cardiac and renal dysfunction associated with a poor prognosis is called cardiorenal syndrome (CRS). CRS not only involves the kidneys and the heart, but also the vascular system, which is the blood-carrying organ in the body. The vascular system is influenced by CRS through hemodynamic, neurohumoral, mechanical and biochemical factors, and by protein-bound uremic toxins. Purinergic signaling is widely accepted as a primitive and highly conserved system among animals, and the roles for nucleotides and nucleosides as extracellular signaling molecules are well described. Over the years, the purinergic system has been significantly implicated in cardiovascular regulation. Nucleotide signaling is known to stimulate vasoconstriction and vasorelaxation, the growth of vascular smooth muscle cells (VSMC) and endothelial cells (EC) and angiogenesis; is involved in vascular remodeling; stimulates platelet aggregation; regulates clotting, inflammation and various aspects of cardiac function. In the vasculature, activation of endothelial P2 receptors induces local vasorelaxation through the production of nitric oxide (NO), prostacyclin (PGI2) and endothelial-derived hyperpolarizing factor (EDHF). In contrast, activation of VSMC P2 receptors promotes vasoconstriction via P2X or P2Y sensitive to pyrimidines. Importantly, ATP and other nucleotides can act via activation of P2 receptors as damage-associated molecular patterns (DAMPs) when released in millimolar concentrations in pathological situations, influencing inflammatory responses. Thus, considering that: 1) the vascular system is also affected by CRS; 2) there are few studies on possible vascular alterations resulting from CRS distant from the site of renal ischemia; and 3) purinergic signaling plays an important role in the regulation of vascular tone and inflammation, the hypothesis of the present study is that vessels distant from the site of renal ischemia, such as the aorta, are functionally altered and such alterations are caused, in part, due to an impairment in the functioning of the P2 receptors present in the vasculature. Therefore, the objective of this work is to characterize the impact of type 3 cardiorenal syndrome, known as acute renocardic syndrome, on the responsiveness of mouse aortae, with emphasis on the participation of the purinergic system. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA, HELEN SOARES VALENCA; RAMOS, LUANA MUNIQUE SOUSA; SILVA, FERNANDA CARDOSO; ALVES, DANIEL LIMA; PEREIRA, GABRIELE DE MENEZES; SANTIAGO, PEDRO HENRIQUE DE OLIVEIRA; DE ALMEIDA, ANGELINA MARIA; ELLENA, JAVIER; CORBI, PEDRO PAULO; OLIVEIRA, CAROLINA GONCALVES; et al. A new copper(II) complex containing long-chain aliphatic hydrazide and 1,10-phenanthroline upregulates ADP hydrolysis in triple-negative breast cancer cells. Journal of Inorganic Biochemistry, v. 255, p. 10-pg., 2024-03-19. (21/10265-8, 19/12219-3, 21/08717-8)

STABILE, JEFERSON; FUERSTENAU, CRISTINA RIBAS. Platelets isolation and ectonucleotidase assay: Revealing functional aspects of the communication between the vasculature and the immune system. JOURNAL OF IMMUNOLOGICAL METHODS, v. 533, p. 13-pg., 2024-08-27. (19/12219-3)

STABILE, JEFERSON; NERES-SANTOS, RAQUEL SILVA; HERNANDES, ISABELA DORTA MOLINA; JUNHO, CAROLINA VICTORIA CRUZ; ALVES, GEOVANE FELIPPE; SILVA, ISABELLA CARDOSO; CARNEIRO-RAMOS, MARCELA SORELLI; FURSTENAU, CRISTINA RIBAS. Renal ischemia and reperfusion impact the purinergic signaling in a vascular bed distant from the injured site. Biochimie, v. 222, p. 8-pg., 2024-02-29. (19/12219-3, 22/00153-0, 19/11077-0)

DA SILVA, FERNANDA CARDOSO; DE ARAUJO, BRUNA JUBER; CORDEIRO, CARINA SANTOS; ARRUDA, VINICIUS MARQUES; FARIA, BRUNO QUINTANILHA; DA COSTA GUERRA, JOYCE FERREIRA; DE ARAUJO, THAISE GONCALVES; FURSTENAU, CRISTINA RIBAS. Endothelial dysfunction due to the inhibition of the synthesis of nitric oxide: Proposal and characterization of an in vitro cellular model. FRONTIERS IN PHYSIOLOGY, v. 13, p. 13-pg., 2022-11-17. (19/12219-3)