Ca2+ mishandling and mitochondrial dysfunction: a converging road to prediabetic and diabetic cardiomyopathy
Carolina Jaquenod De Giusti1, Julieta Palomeque1, Alicia Mattiazzi2
1Centro de Investigaciones Cardiovasculares, CCT-La Plata-CONICET, Facultad de Cs. Médicas, UNLP, La Plata, Argentina.
Insights
Diabetic cardiomyopathy, a silent heart dysfunction in diabetes mellitus (DM), is poorly recognized in early stages. This review explores key early mechanisms, including calcium mishandling and mitochondrial dysfunction, crucial for timely diagnosis and treatment.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Diabetic cardiomyopathy (DCM) is myocardial dysfunction in diabetes mellitus (DM) without hypertension or structural heart disease.
- Early DCM, including prediabetes, is often asymptomatic and undiagnosed until severe dysfunction occurs.
- Understanding early pathophysiological mechanisms is vital for timely diagnosis and treatment of DCM.
Purpose of the Study:
- To review the pivotal early pathophysiological mechanisms in diabetic cardiomyopathy.
- To focus on calcium (Ca2+) mishandling and mitochondrial dysfunction in early DCM.
- To explore the molecular pathways linking Ca2+ and mitochondrial alterations in DCM development.
Main Methods:
- Literature review focusing on molecular and cellular mechanisms of DCM.
- Analysis of studies investigating calcium handling and mitochondrial function in diabetic hearts.
- Synthesis of current understanding of the interplay between Ca2+ and mitochondria in early DCM.
Main Results:
- Calcium mishandling is a key early event in DCM.
- Mitochondrial dysfunction significantly contributes to the development of DCM.
- Specific molecular pathways link Ca2+ dysregulation and mitochondrial impairment in DCM.
Conclusions:
- Early recognition of DCM requires understanding Ca2+ mishandling and mitochondrial dysfunction.
- Targeting these early molecular pathways may offer novel therapeutic strategies for DCM.
- Further research into the Ca2+-mitochondria interplay is crucial for preventing and treating diabetic heart disease.
Abstract:
Diabetic cardiomyopathy is defined as the myocardial dysfunction that suffers patients with diabetes mellitus (DM) in the absence of hypertension and structural heart diseases such as valvular or coronary artery dysfunctions. Since the impact of DM on cardiac function is rather silent and slow, early stages of diabetic cardiomyopathy, known as prediabetes, are poorly recognized, and, on many occasions, cardiac illness is diagnosed only after a severe degree of dysfunction was reached. Therefore, exploration and recognition of the initial pathophysiological mechanisms that lead to cardiac dysfunction in diabetic cardiomyopathy are of vital importance for an on-time diagnosis and treatment of the malady. Among the complex and intricate mechanisms involved in diabetic cardiomyopathy, Ca2+ mishandling and mitochondrial dysfunction have been described as pivotal early processes. In the present review, we will focus on these two processes and the molecular pathway that relates these two alterations to the earlier stages and the development of diabetic cardiomyopathy.
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