Effects of Bergamot Polyphenols on Mitochondrial Dysfunction and Sarcoplasmic Reticulum Stress in Diabetic Cardiomyopathy

Abstract

Cardiovascular disease is the leading cause of death and disability in the Western world. In order to safeguard the structure and the functionality of the myocardium, it is extremely important to adequately support the cardiomyocytes. Two cellular organelles of cardiomyocytes are essential for cell survival and to ensure proper functioning of the myocardium: mitochondria and the sarcoplasmic reticulum. Mitochondria are responsible for the energy metabolism of the myocardium, and regulate the processes that can lead to cell death. The sarcoplasmic reticulum preserves the physiological concentration of the calcium ion, and triggers processes to protect the structural and functional integrity of the proteins. The alterations of these organelles can damage myocardial functioning. A proper nutritional balance regarding the intake of macronutrients and micronutrients leads to a significant improvement in the symptoms and consequences of heart disease. In particular, the Mediterranean diet, characterized by a high consumption of plant-based foods, small quantities of red meat, and high quantities of olive oil, reduces and improves the pathological condition of patients with heart failure. In addition, nutritional support and nutraceutical supplementation in patients who develop heart failure can contribute to the protection of the failing myocardium. Since polyphenols have numerous beneficial properties, including anti-inflammatory and antioxidant properties, this review gathers what is known about the beneficial effects of polyphenol-rich bergamot fruit on the cardiovascular system. In particular, the role of bergamot polyphenols in mitochondrial and sarcoplasmic dysfunctions in diabetic cardiomyopathy is reported.

Keywords: bergamot polyphenolic fraction; bergamot polyphenols; diabetic cardiomyopathy; myocardial dysfunction; myocardial metabolism; role of mitochondria and sarcoplasmic reticulum in the myocardium.

Figure 1

Characteristics of systemic, organ (myocardium), and cellular (cardiomyocytes) diabetic cardiomyopathy.

Figure 2

Involvement of mitochondria and sarcoplasmic reticulum in stress induced by diabetic cardiomyopathy, showing how diabetes, hyperglycemia, hyperinsulinemia, and hyperlipidemia cause a stress condition involving dysfunction of the mitochondria and sarcoplasmic reticulum. In particular, some events occur including an impaired calcium homeostasis, altered protein expression, autophagy, and apoptotic cell death.

Figure 3

Steps involved in diabetic cardiomyopathy in temporal order. (1) Downregulation of SERCA pump in the sarcoplasmic reticulum; (2) mitochondrion downregulation; (3) consequent increase in cytosolic calcium; (4) accumulation of oxidative stress in cells; (5) increase in lipotoxicity; (6) increase in advanced glycation products; (7) inflammation; (8) rearrangement of myocardial tissue with hypertrophy and fibrosis; (9) onset of diastolic dysfunction.