Flávio Reis

By Helena M. Teixeira and Flávio Reis

Part of the book: Forensic Medicine

By Sandra Ribeiro, Luís Belo, Flávio Reis and Alice Santos‐Silva

Anemia is a common complication of chronic kidney disease (CKD) associated with disease progression and increased mortality. This anemia is mainly due to inadequate production of erythropoietin (EPO) by the failing kidneys, resulting from the reduction in renal EPO‐producing cells (REPC) or from dysregulation of the hypoxia‐inducible factor (HIF) system that regulates several genes related to hypoxia, angiogenesis, fibrosis and glucose metabolism, among others. In this chapter, we present a review on the HIF system in CKD‐anemia, the HIF response to erythropoiesis‐stimulating agents (ESA) therapy and its potential involvement in the development of ESA resistance by enhancing kidney fibrosis and inflammation. Due to concerns related to ESA use, new drugs to correct anemia are under study, being the prolyl hydroxylase inhibitors the most promising candidates.

Part of the book: Hypoxia and Human Diseases

By Sara Nunes, Anabela Pinto Rolo, Carlos Manuel Palmeira and Flávio Reis

Diabetic cardiomyopathy (DCM) is an independent clinical entity defined as structural and functional changes in the myocardium because of metabolic and cellular abnormalities induced by diabetes, resulting in cardiac failure. Hyperglycemia has been seen as a major cause of DCM due to activation of different mechanisms leading to oxidative stress. Several body of evidence show that distinct pathways of oxygen and nitrogen reactive species formation contribute to myocardial impairment. Abnormal mitochondrial morphology and energetics, evoked by abnormal Ca2+ handling, metabolic changes and oxidative stress, are observed in DCM, suggesting a pivotal role of mitochondrial dynamics in disease pathogenesis. In addition, insulin resistance compromises myocardial glucose uptake due to cellular depletion of glucose transporter proteins, together with increased myocardial uptake of free fatty acids and augmented triglyceride levels, which cause cardiomyocyte lipotoxicity. Finally, the state of chronic low-grade inflammation, a feature of obese type 2 diabetes, seems to also play a major role in DCM progression, whose mechanisms have been progressively disclosed. In this book chapter, we review the cellular mechanism contributing to DCM development, focusing on oxidative stress, mitochondrial dysfunction and inflammation of cardiomyocytes, as well as on possible therapeutic strategies.

Part of the book: Cardiomyopathies