Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with...Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus (DM). AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modification of the structure, function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs (RAGE)]. A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure. Moreover, some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with heart failure (HF). The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure, focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.展开更多
Heart failure (HF) and atrial fibrillation (AF) frequently coexist and have emerged as major cardiovascular epidemics. There is growing evidence that AF is an independent prognostic marker in HF and affects patients w...Heart failure (HF) and atrial fibrillation (AF) frequently coexist and have emerged as major cardiovascular epidemics. There is growing evidence that AF is an independent prognostic marker in HF and affects patients with both reduced as well as preserved LV systolic function. There has been a general move in clinical practice from a rhythm control to a rate control strategy in HF patients with AF, although recent data suggests that rhythm control strategies may provide better outcomes in selected subgroups of HF patients. Furthermore, various therapeutic modalities including pace and ablate strategies with cardiac resynchronisation or radio-frequency ablation have become increasingly adopted, although their role in the management of AF in patients with HF remains uncertain. This article presents an overview of the multidimensional impact of AF in patients with HF. Relevant literature is highlighted and the effect of various therapeutic modalities on prognosis is discussed. Finally, while novel anticoagulants usher in a new era in thromboprophylaxis, research continues in avariety of new pathways including selective atrial anti-arrhythmic agents and genomic polymorphisms in AF with HF.展开更多
Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathw...Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular freecalcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulindependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.展开更多
The plasma membrane calcium ATPases(PMCA) are a family of genes which extrude Ca2+from the cell and are involved in the maintenance of intracellular free calcium levels and/or with Ca2+signalling,depending on the cell...The plasma membrane calcium ATPases(PMCA) are a family of genes which extrude Ca2+from the cell and are involved in the maintenance of intracellular free calcium levels and/or with Ca2+signalling,depending on the cell type.In the cardiovascular system,Ca2+ is not only essential for contraction and relaxation but also has a vital role as a second messenger in signal transduction pathways.A complex array of mechanisms regulate intracellular free calcium levels in the heart and vasculature and a failure in these systems to maintain normal Ca2+homeostasis has been linked to both heart failure and hypertension.This article focuses on the functions of PMCA,in particular isoform 4(PMCA4) ,in the heart and vasculature and the reported links between PMCAs and contractile function,cardiac hypertrophy,cardiac rhythm and sudden cardiac death,and blood pressure control and hypertension.It is becoming clear that this family of calcium extrusion pumps have essential roles in both cardiovascular health and disease.展开更多
文摘Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus (DM). AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modification of the structure, function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs (RAGE)]. A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure. Moreover, some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with heart failure (HF). The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure, focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.
文摘Heart failure (HF) and atrial fibrillation (AF) frequently coexist and have emerged as major cardiovascular epidemics. There is growing evidence that AF is an independent prognostic marker in HF and affects patients with both reduced as well as preserved LV systolic function. There has been a general move in clinical practice from a rhythm control to a rate control strategy in HF patients with AF, although recent data suggests that rhythm control strategies may provide better outcomes in selected subgroups of HF patients. Furthermore, various therapeutic modalities including pace and ablate strategies with cardiac resynchronisation or radio-frequency ablation have become increasingly adopted, although their role in the management of AF in patients with HF remains uncertain. This article presents an overview of the multidimensional impact of AF in patients with HF. Relevant literature is highlighted and the effect of various therapeutic modalities on prognosis is discussed. Finally, while novel anticoagulants usher in a new era in thromboprophylaxis, research continues in avariety of new pathways including selective atrial anti-arrhythmic agents and genomic polymorphisms in AF with HF.
基金Supported by The Breast Cancer Campaign and the Research Institute in Healthcare Sciences (Armesilla AL)The Wellcome Trust (Emerson M)
文摘Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular freecalcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulindependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.
文摘The plasma membrane calcium ATPases(PMCA) are a family of genes which extrude Ca2+from the cell and are involved in the maintenance of intracellular free calcium levels and/or with Ca2+signalling,depending on the cell type.In the cardiovascular system,Ca2+ is not only essential for contraction and relaxation but also has a vital role as a second messenger in signal transduction pathways.A complex array of mechanisms regulate intracellular free calcium levels in the heart and vasculature and a failure in these systems to maintain normal Ca2+homeostasis has been linked to both heart failure and hypertension.This article focuses on the functions of PMCA,in particular isoform 4(PMCA4) ,in the heart and vasculature and the reported links between PMCAs and contractile function,cardiac hypertrophy,cardiac rhythm and sudden cardiac death,and blood pressure control and hypertension.It is becoming clear that this family of calcium extrusion pumps have essential roles in both cardiovascular health and disease.
