Journal
FRONTIERS IN CARDIOVASCULAR MEDICINE
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcvm.2021.810791
Keywords
sodium-glucose cotransporter 2 inhibitor; heart failure; diabetes; clinical trials; sodium and calcium overload
Categories
Funding
- Italian Ministry of Education, the University and Research grants [PRIN-2017XZMBYX, PRIN-2017NKB2N4]
Ask authors/readers for more resources
Type 2 diabetes mellitus (T2DM) and heart failure (HF) are multifactorial diseases with common risk factors and underlying mechanisms; The cardiovascular benefits of SGLT2 inhibitors may be related to their cardiac-specific mechanisms; Research suggests that reducing intracellular sodium levels is a key mechanism for the direct cardiac effects of SGLT2 inhibitors.
Type 2 diabetes mellitus (T2DM) and heart failure (HF) are multifactorial diseases sharing common risk factors, such as obesity, hyperinsulinemia, and inflammation, with underlying mechanisms including endothelial dysfunction, inflammation, oxidative stress, and metabolic alterations. Cardiovascular benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors observed in diabetic and non-diabetic patients are also related to their cardiac-specific, SGLT-independent mechanisms, in addition to the metabolic and hemodynamic effects. In search of the possible underlying mechanisms, a research campaign has been launched proposing varied mechanisms of action that include intracellular ion homeostasis, autophagy, cell death, and inflammatory processes. Moreover, the research focus was widened toward cellular targets other than cardiomyocytes. At the moment, intracellular sodium level reduction is the most explored mechanism of direct cardiac effects of SGLT2 inhibitors that mediate the benefits in heart failure in addition to glucose excretion and diuresis. The restoration of cardiac Na+ levels with consequent positive effects on Ca2+ handling can directly translate into improved contractility and relaxation of cardiomyocytes and have antiarrhythmic effects. In this review, we summarize clinical trials, studies on human cells, and animal models, that provide a vast array of data in support of repurposing this class of antidiabetic drugs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available