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Mechanisms of Heart Failure pp 185–195Cite as

Myocardial Lipid Peroxidation and Diabetes

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Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 167))

Summary

Diabetic patients develop cardiomyopathy, characterized mainly by left ventricular contractile dysfunction and congestive heart failure. Vitamin E-quinone and lipid peroxidation levels in the heart ventricles are signi ficantly higher in diabetic rats compared with control rats. This increase was prevented in insulin-treated diabetic rats. Hyperglycemia can generate oxygen radicals and cause membrane lipid peroxidation in the myocardium. Lipid peroxidation and its products can cause hyperviscosity and hypercoagulability of blood, and oxidative modification of lipoproteins. This can result in altered blood, and atherosclerosis. On the other hand, lipid peroxides can inhibit prostacyclin synthetase and causes imbalance in the prostacyclin and thromboxane levels, which can induce vasoconstriction. Thus, increased lipid peroxidation may have a role in the altered contractile property of heart ventricles and the development of cardiomyopathy associated with diabetes.

Diabetes mellitus has been listed as the seventh leading cause of death and is frequently associated with cardiovascular disease [1]. The reasons for increased cardiovascular disease in diabetic patients are not completely understood. Many epidemiologic studies provide evidence that poor glycémie control in diabetic patients significantly increases their risk for coronary heart disease. Risk factors, such as oxidation of lipoproteins, protein glycation, and hypercoagulability of blood, are direct consequences of hyperglycemia and contribute in varying degrees to the development of cardiovascular disease in diabetes mellitus [2].

Recently, Morel and Chislom [3] have observed oxidized lipoproteins in diabetic rats with obvious implications for atherogenesis and cardiovascular disease. Oxidized low-density lipoprotein (LDL) is cytotoxic and is likely to be responsible for foam cell necrosis and the development of an extracellular lipid core and atherosclerotic lesions [4].

Platelets from diabetic subjects exhibit enhanced adhesiveness, increased aggregability to various agonists, decreased survival, and increased generation of thromboxane [5-7]. Thromboxane is known to induce not only aggregation, but also vasoconstrictor activity [7]. At least some of these functional changes may be a result of the nonenzymatic glycation of platelet proteins, particularly glycoproteins, and the altered phospholipid asymmetry of platelets in diabetes [5-8]. Similarly, erythrocytes of diabetic patients are known to have several abnormalities, such as excessive aggregation, reduced deformability, hyperviscosity, glycosylation of proteins, sorbitol accumulation, oxidative damage, phosphatidylserine (PS) externalization in the outer membrane bilayer, and increased adhesivity to endothelial cells and its relation to the vascular complications [9-19]. It is suggested that both platelets and erythrocytes are involved in endothelial alteration, platelet deposition, and atherosclerotic processes and the impairment of diabetic microvascular flow and complications [20].

Thus, at least some risk of development of cardiovascular disease may be genetic, others are associated with increased glycation of proteins, and some may be associated with the activation of aldose reductase caused by hyperglycemia. This chapter discusses the association between the cardiomyopathy of diabetes and the increased activity of reactive oxygen species and oxidative cellular damage.

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Authors
  1. Sushil K. Jain
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  1. MRC Group in Experimental Cardiology Division of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Pawan K. Singal , Ian M. C. Dixon , Robert E. Beamish  & Naranjan S. Dhalla , ,  & 

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Jain, S.K. (1995). Myocardial Lipid Peroxidation and Diabetes. In: Singal, P.K., Dixon, I.M.C., Beamish, R.E., Dhalla, N.S. (eds) Mechanisms of Heart Failure. Developments in Cardiovascular Medicine, vol 167. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2003-0_16

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  • DOI: https://doi.org/10.1007/978-1-4615-2003-0_16

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