Oxidative stress and heart failure in altered thyroid States

Abstract

Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that hyperthyroidism induces a hyperdynamic cardiovascular state, which is associated with a faster heart rate, enhanced left ventricular systolic and diastolic function whereas hypothyroidism is characterized by the opposite changes. Hyperthyroidism and hypothyroidism represent opposite clinical conditions, albeit not mirror images. Recent experimental and clinical studies have suggested the involvement of ROS tissue damage under altered thyroid status. Altered-thyroid state-linked changes in heart modify their susceptibility to oxidants and the extent of the oxidative damage they suffer following oxidative challenge. Chronic increase in the cellular levels of ROS can lead to a catastrophic cycle of DNA damage, mitochondrial dysfunction, further ROS generation and cellular injury. Thus, these cellular events might play an important role in the development and progression of myocardial remodeling and heart failure in altered thyroid states (hypo- and hyper-thyroidism). The present review aims at elucidating the various signaling pathways mediated via ROS and their modulation under altered thyroid state and the possibility of antioxidant therapy.

Figure 1

Effects of thyroid hormone on cardiac function.

Figure 2

Potential sources of reactive oxygen species (ROS) and their effects on cardiac function. Cytp450: cytochrome p450, NOS: nitric oxide synthase, PDGF: platelet-derived growth factor, TNF-α: tumor necrosis factor, ASK-I: apoptosis-regulating signal kinase, MAPK: mitogen-activated protein kinases, NFκB: nuclear factor κB, MMP: matrix metalloproteinase, AngII: Angiotension II, ATIR: Angiotension I receptor, and SERCA: sarcoplasmic endoplasmin reticulum calcium ATPase.

Figure 3

Cardiac oxidative stress under altered thyroid states.