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The Adaptive Immune Role of Metallothioneins in the Pathogenesis of Diabetic Cardiomyopathy: Good or Bad



The Adaptive Immune Role of Metallothioneins in the Pathogenesis of Diabetic Cardiomyopathy: Good or Bad



American Journal of Physiology. Heart and Circulatory Physiology 2019



Diabetes is a metabolic disorder characterized by hyperglycemia, resulting in low-grade systemic inflammation. Diabetic cardiomyopathy (DCM) is a common complication among diabetes patients, and the mechanism underlying its induction of cardiac remodeling and dysfunction remains unclear. Numerous experimental and clinical studies suggested that adaptive immunity, especially T lymphocyte-mediated immunity, plays a potentially important role in in the pathogenesis of diabetes and DCM. Metallothioneins (MTs), cysteine-rich metal-binding proteins, have antioxidant properties. Some potential mechanisms underlying the cardioprotective effects of MTs include the role of MTs in calcium regulation, zinc homeostasis, insulin sensitization, and antioxidant activity. Moreover, metal homeostasis, especially MT-regulated zinc homeostasis, is essential for immune function. This review discusses aberrant immune regulation in diabetic heart disease with respect to endothelial insulin resistance and the effects of hyperglycemia and hyperlipidemia on tissues and the different effects of intracellular and extracellular MTs on adaptive immunity. This review shows that intracellular MTs are involved in naïve T cell activation and reduce Treg polarization, while extracellular MTs promote proliferation and survival in naïve T cells and Treg polarization but inhibit their activation, thus revealing potential therapeutic strategies targeting the regulation of immune cell function by MTs.

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Accession: 066793864

Download citation: RISBibTeXText

PMID: 31100011

DOI: 10.1152/ajpheart.00123.2019


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