Pathophysiological Fundamentals of Diabetic Cardiomyopathy

Abstract

Diabetic cardiomyopathy (DCM) was first recognized more than four decades ago and occurred independent of cardiovascular diseases or hypertension in both type 1 and type 2 diabetic patients. The exact mechanisms underlying this disease remain incompletely understood. Several pathophysiological bases responsible for DCM have been proposed, including the presence of hyperglycemia, nonenzymatic glycosylation of large molecules (e.g., proteins), energy metabolic disturbance, mitochondrial damage and dysfunction, impaired calcium handling, reactive oxygen species formation, inflammation, cardiac cell death, and cardiac hypertrophy and fibrosis, leading to impairment of cardiac contractile functions. Increasing evidence also indicates the phenomenon called "metabolic memory" for diabetes-induced cardiovascular complications, for which epigenetic modulation seemed to play an important role, suggesting that the aforementioned pathogenic bases may be regulated by epigenetic modification. Therefore, this review aims at briefly summarizing the current understanding of the pathophysiological bases for DCM. Although how epigenetic mechanisms play a role remains incompletely understood now, extensive clinical and experimental studies have implicated its importance in regulating the cardiac responses to diabetes, which are believed to shed insight into understanding of the pathophysiological and epigenetic mechanisms for the development of DCM and its possible prevention and/or therapy. © 2017 American Physiological Society. Compr Physiol 7:693-711, 2017.

LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

“…DCM results in a high-risk of heart failure, arrhythmia and sudden death, and is the major cause of mortality in patients with diabetes [3,4]. The pathogenesis of DCM includes altered metabolism, mitochondrial dysfunction, oxidative stress, inflammation, cell death and remodeling of the extracellular matrix [5]. However, the diagnosis and therapy of DCM are limited because the molecular mechanisms of DCM remain elusive.…”

Silymarin ameliorates diabetic cardiomyopathy via inhibiting TGF‐β1/Smad signaling

“…DM is characterized by high blood glucose and leads to multiple complications including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy (Baba and Ishizaki, 1992;Chen et al, 2017;Hung et al, 2017;Ung et al, 2017). Of these, DCM is a major complication, causing high morbidity and mortality (Frati et al, 2017;Gilca et al, 2017;Hu et al, 2017). Evidence indicates that Chinese traditional medicine and phytomedicine have beneficial effects on diabetic complications including DCM.…”

Long noncoding RNAs: A new player in the prevention and treatment of diabetic cardiomyopathy?

“…With the continuous deepening of diabetes research, people's research on diabetes and its complications has entered the genetic level. More and more studies have shown that noncoding RNA (ncRNA) plays a vital role in the occurrence and development of DCM . For example, microRNAs (miRNAs, miRs) play an essential role in the incident and development of DCM .…”

“…The typical morphological features of apoptosis are DNA fragmentation, rounding of cell shrinkage, condensation of chromatin, vacuolation of the membrane, nuclear condensation, and small apoptosis. The signal transduction pathways are mainly intrinsic pathways, also known as mitochondrial pathways; exogenous pathways, also known as death receptor pathways; and ER pathways . Autophagy is an active process of cell death mediated by cellular signalling pathways.…”

“…[11][12][13][14][15][16] For example, microRNAs (miRNAs, miRs) play an essential role in the incident and development of DCM. 3,11,14,17 However, as we have seen, the study of the relationship between lncRNA and DCM is almost blank. Therefore, it is necessary to summarize the researches on the occurrence and development of lncRNA in DCM, to provide potential inspiration for DCM's future prevention and treatment strategies.…”