During the course of normal respiration, reactive oxygen species are produced which are particularly detrimental to mitochondrial function. This is shown by recent studies with a mouse that lacks the mitochondrial form of superoxide dismutase (Sod2). Tissues that are heavily dependent on mitochondrial function such as the brain and heart are most severely affected in the Sod2 mutant mouse.
Clinical and Experimental Pharmacology & Physiology
SUMMARY: The contractile function of the heart requires the release of Ca(2+) from intracellular Ca(2+) stores in the sarcoplasmic reticulum (SR) of cardiac muscle cells. The efficacy of Ca(2+) release depends on the amount of Ca(2+) loaded into the Ca(2+) store and the way in which this 'Ca(2+) load' influences the activity of the cardiac ryanodine receptor Ca(2+) release channel (RyR2).
Cardiac fibrosis is critically involved in the adverse remodeling accompanying dilated cardiomyopathies (DCMs), which leads to cardiac dysfunction and heart failure (HF). Connective tissue growth factor (CTGF), a profibrotic cytokine, plays a key role in this deleterious process. Some beneficial effects of IGF1 on cardiomyopathy have been described, but its potential role in improving DCM is less well characterized.
The extracellular matrix (ECM) provides structural support by serving as a scaffold for cells, and as such the ECM maintains normal tissue homeostasis and mediates the repair response following injury. In response to myocardial infarction (MI), ECM expression is generally upregulated in the left ventricle (LV), which regulates LV remodeling by modulating scar formation. The ECM directly affects scar formation by regulating growth factor release and cell adhesion and indirectly affects scar formation by regulating the inflammatory, angiogenic, and fibroblast responses.
Laboratory Investigation; a Journal of Technical Methods and Pathology
The protective effect of heme oxygenase-1 (HO-1) expression in cardiovascular disease has been previously demonstrated using transgenic animal models in which HO-1 is constitutively overexpressed in the heart. However, the temporal requirements for protection by HO-1 induction relative to injury have not been investigated, but are essential to employ HO-1 as a therapeutic strategy in human cardiovascular disease states.
Chronic caloric restriction (CR) has been demonstrated to increase longevity in lower species and studies are ongoing to evaluate its effect in higher species. A consistent metabolic feature of CR is improved insulin sensitivity and lowered lifetime glycemia, yet the mechanism responsible is currently unknown. However, the membrane's physiochemical properties, as determined by phospholipid composition, have been related to insulin action in animal and human studies and CR has been reported to alter membrane lipid content.
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
BACKGROUND: Aging is a complex multifactorial process characterized by accumulation of deleterious changes in cells and tissues, progressive deterioration of structural integrity and physiological function across multiple organ systems, and increased risk of death. METHODS: We conducted a review of the scientific literature on the relationship of advanced glycation end products (AGEs) with aging. AGEs are a heterogeneous group of bioactive molecules that are formed by the nonenzymatic glycation of proteins, lipids, and nucleic acids.
Myocardial ischemia followed by ischemia/reperfusion (I/R) induces irreversible damage to cardiac muscle. Medical treatment that effectively prevents I/R injury would alleviate the consequent development of cardiac remodeling and failure. Mechanisms that extend life span often make organisms resistant to stress, and an accumulation of such mechanisms may prevent aging and susceptibility to age-associated diseases. Sirtuins are a group of molecules involved in longevity and stress resistance.