Abstract
Cardiovascular complications are the leading cause of death and morbidity in patients with diabetes; accounting for around 7 out of 10 of all causes of death in this population. Returning patients to normoglycaemia alone has been shown to have little effect on cardiovascular end points, therefore new therapies and strategies are required in order to reduce the incidence and improve outcomes of cardiovascular disease in diabetic individuals. The metabolic enzyme AMP-activated protein kinase (AMPK) has emerged in recent years as an attractive potential therapeutic target for diabetic vascular disease, and studies have shown improved endothelial and smooth muscle cell function following AMPK activation. Additionally, improved lipid profiles, reduced hypertrophic cardiomyocyte growth and protection from cardiac ischaemia-reperfusion injury have also been observed as beneficial outcomes of AMPK therapy. In this review we will discuss in detail the potential downstream targets of AMPK activation in the cardiovascular system. We will also provide an overview of long-known and newly discovered direct and indirect AMPK activators, as well as novel synthesised AMPK-activating compounds, which will highlight the potential for further exploiting AMPK in a therapeutic context for cardiovascular disease in diabetes.
Keywords: A-769662, AICAR, AMPK, cardiac, cardiovascular, CVD, diabetes, endothelium, lipids, metformin, restenosis, smooth muscle, statins, thiazolidinediones
Cardiovascular & Hematological Agents in Medicinal Chemistry
Title:Diabetic Cardiovascular Disease – AMP-Activated Protein Kinase (AMPK) as a Therapeutic Target
Volume: 10 Issue: 3
Author(s): Marie-Ann Ewart and Simon Kennedy
Affiliation:
Keywords: A-769662, AICAR, AMPK, cardiac, cardiovascular, CVD, diabetes, endothelium, lipids, metformin, restenosis, smooth muscle, statins, thiazolidinediones
Abstract: Cardiovascular complications are the leading cause of death and morbidity in patients with diabetes; accounting for around 7 out of 10 of all causes of death in this population. Returning patients to normoglycaemia alone has been shown to have little effect on cardiovascular end points, therefore new therapies and strategies are required in order to reduce the incidence and improve outcomes of cardiovascular disease in diabetic individuals. The metabolic enzyme AMP-activated protein kinase (AMPK) has emerged in recent years as an attractive potential therapeutic target for diabetic vascular disease, and studies have shown improved endothelial and smooth muscle cell function following AMPK activation. Additionally, improved lipid profiles, reduced hypertrophic cardiomyocyte growth and protection from cardiac ischaemia-reperfusion injury have also been observed as beneficial outcomes of AMPK therapy. In this review we will discuss in detail the potential downstream targets of AMPK activation in the cardiovascular system. We will also provide an overview of long-known and newly discovered direct and indirect AMPK activators, as well as novel synthesised AMPK-activating compounds, which will highlight the potential for further exploiting AMPK in a therapeutic context for cardiovascular disease in diabetes.
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Cite this article as:
Ewart Marie-Ann and Kennedy Simon, Diabetic Cardiovascular Disease – AMP-Activated Protein Kinase (AMPK) as a Therapeutic Target, Cardiovascular & Hematological Agents in Medicinal Chemistry 2012; 10 (3) . https://dx.doi.org/10.2174/187152512802651015
DOI https://dx.doi.org/10.2174/187152512802651015 |
Print ISSN 1871-5257 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6182 |
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Medicinal Plants with Beneficial Properties on Diabetes and Hypertension
Diabetes and hypertension are real scourges of the 21st century. It is imperative to act in order to find innovative solutions to this problem. Taking medications such as hypoglycemic and antihypertensive drugs may aggravate certain underlying comorbidities, such as chronic kidney disease and cardiovascular disease. This significant drawback therefore requires ...read more
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