Mechanisms and Therapeutic Prospects of Diabetic Cardiomyopathy Through the Inflammatory Response

Abstract

The incidence of heart failure (HF) continues to increase rapidly in patients with diabetes. It is marked by myocardial remodeling, including fibrosis, hypertrophy, and cell death, leading to diastolic dysfunction with or without systolic dysfunction. Diabetic cardiomyopathy (DCM) is a distinct myocardial disease in the absence of coronary artery disease. DCM is partially induced by chronic systemic inflammation, underpinned by a hostile environment due to hyperglycemia, hyperlipidemia, hyperinsulinemia, and insulin resistance. The detrimental role of leukocytes, cytokines, and chemokines is evident in the diabetic heart, yet the precise role of inflammation as a cause or consequence of DCM remains incompletely understood. Here, we provide a concise review of the inflammatory signaling mechanisms contributing to the clinical complications of diabetes-associated HF. Overall, the impact of inflammation on the onset and development of DCM suggests the potential benefits of targeting inflammatory cascades to prevent DCM. This review is tailored to outline the known effects of the current anti-diabetic drugs, anti-inflammatory therapies, and natural compounds on inflammation, which mitigate HF progression in diabetic populations.

Cannabinoid 2 receptor agonist and L-arginine combination attenuates diabetic cardiomyopathy in rats via NF-ĸβ inhibition

“…The pathophysiology of DCM is well established by various pre-clinical and clinical research. Hyperglycemia is a hallmark of diabetes; which is a very well-known risk factor in the development of DCM, which is attributed to cardiac hypertrophy, vascular endothelial dysfunction, increased oxidative stress, inflammation and mitochondrial dysfunction (Knapp, Tu and Wu, 2019;Paolillo et al, 2019;Kaur et al, 2021). Collectively, all these factors contribute to the accumulation of pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6) and transforming growth factor-beta (TGF-β) in the cardiac tissue that can induce the cardiac injury.…”

Role of circulating molecules in age-related cardiovascular and metabolic disorders

“…Level of pro-inflammatory cytokines such as interleukin-6 (IL-6), IL-1β, tumor necrosis factor α (TNF-α), and C-reactive protein (CRP), molecules contributing to the enhancement of inflammation including soluble intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) increase in circulation with chronological aging [ 49 – 52 ]. Chronic low-grade sterile inflammation associates with the production of reactive oxygen species (ROS), mitochondrial dysfunction, and cellular senescence and promotes pathologies in cardiovascular-metabolic disorders [ 8 , 53 ].…”

Editorial: Metabolic Related Cardiomyopathy in Hyperglycemic Patients

“…In particular, DCM is associated with cardiac hypertrophy and fibrosis with consequent cardiomyocyte cell death. Those tissue events are also a consequence of a pro-inflammatory cascade ( 5 ) encompassing the release of TBF-a, IL1b, and IL-6 and leukocyte activation, associated with an activation of nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB). This may lead to an auto-potentiating vicious cycle that is activated between cardiomyocytes cell metabolic mediated auto-degeneration and pro-inflammatory mechanisms.…”

“…Myocardial inflammation has been shown to play a critical role in the pathogenesis of HF with reduced and preserved ejection fraction. Systemic and tissue inflammation is very often associated with abnormal cardiac function and structure (5)(6)(7). From a physio-pathological point of view, hyperinsulinemia, hyperglycemia, hyperlipidemia, and insulin resistance may conspire to the genesis and worsening of DCM leading to HF.…”