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Diabetic heart disease (DHD) is the leading cause of morbidity and mortality among the people with diabetes, with approximately 80% of the deaths in diabetics are due to cardiovascular complications. Importantly, heart disease in the diabetics develop at a much earlier stage, although remaining asymptomatic till the later stage of the disease, ther...
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... Cardiac disease that develops as a direct consequence of DM in patients with type 1 DM (T1DM) or type 2 DM (T2DM), known as diabetic heart disease, has characteristic molecular, structural, and functional changes in the myocardium [4]. Diabetes confers a 1.4-and 1.6-fold risk of CVD for men and women after adjusting for other associated conditions, respectively [5]. ...
... Their regulation is based on the repression of translation and on promoting the degradation of target messenger ribonucleic acids (mRNAs). Changes in miRNA levels can play a crucial role in progressive dilated cardiomyopathy and heart failure [113]. ...
Cardiovascular diseases and diabetes mellitus are currently among the diseases with the highest morbidity and mortality. The pathogenesis and development of these diseases remain strongly connected, along with inflammation playing a major role. Therefore, the treatment possibilities showing a positive impact on both of these diseases could be especially beneficial for patients. SGLT-2 inhibitors and GLP-1 receptor agonists present this dual effect. Moreover, the hostile composition of the gut microbiota could influence the progression of these conditions. In this review, the authors present the latest knowledge on and innovations in diabetes mellitus and CVD—with the focus on the molecular mechanisms and the role of the microbiota.
... These changes in heart tissue are considered a sign of heart fibrosis, so proteins, mRNAs, and other molecules mentioned as biomarkers of heart fibrosis can be employed in studies. Along with various molecules and properties, μRNAs have recently shown great potential to be considered as biomarkers in studying diseases, such as diabetes and heart failure, such as ischemic heart disease [172]. In this study, in addition to the usual markers of cardiac fibrosis, differences in the expression of different mRNAs in cardiac fibrosis tissue and healthy tissue were investigated. ...
... In Tables 4 and 5, the biomarkers examined in recent HOCs are listed. At present, biomarkers are routinely analyzed by various tests, such as western blotting, RT-PCR, and Enzyme-Linked Immunosorbent Assay (ELISA) [156,170,172]. In addition to these standard tests, biosensor devices have recently been designed to measure biomarkers in HOC devices in real-time. ...
Cardiovascular diseases are caused by hereditary factors, environmental conditions, and medication-related issues. On the other hand, the cardiotoxicity of drugs should be thoroughly examined before entering the market. In this regard, heart-on-chip (HOC) systems have been developed as a more efficient and cost-effective solution than traditional methods, such as 2D cell culture and animal models. HOCs must replicate the biology, physiology, and pathology of human heart tissue to be considered a reliable platform for heart disease modeling and drug testing. Therefore, many efforts have been made to find the best methods to fabricate different parts of HOCs and to improve the bio-mimicry of the systems in the last decade. Beating HOCs with different platforms have been developed and techniques, such as fabricating pumpless HOCs, have been used to make HOCs more user-friendly systems. Recent HOC platforms have the ability to simultaneously induce and record electrophysiological stimuli. Additionally, systems including both heart and cancer tissue have been developed to investigate tissue-tissue interactions' effect on cardiac tissue response to cancer drugs. In this review, all steps needed to be considered to fabricate a HOC were introduced, including the choice of cellular resources, biomaterials, fabrication techniques, biomarkers, and corresponding biosensors. Moreover, the current HOCs used for modeling cardiac diseases and testing the drugs are discussed. We finally introduced some suggestions for fabricating relatively more user-friendly HOCs and facilitating the commercialization process.
... In general, suppression of the upregulated miRs and activation of downregulated miRs in DCM milieu could serve as a therapeutic approach. Among aforementioned miRs, miR-223, miR-1, miR-499, and miR-133a have been shown to be involved in the post-translational modulation of several kinases in diabetic conditions [163,176,178]. In particular, miR-223 (remains upregulated in DCM) plays a crucial role in the pathogenesis of DCM. ...
Diabetes mellitus (DM) and cardiovascular complications are two unmet medical emergencies that can occur together. The rising incidence of heart failure in diabetic populations, in addition to apparent coronary heart disease, ischemia, and hypertension-related complications, has created a more challenging situation. Diabetes, as a predominant cardio-renal metabolic syndrome, is related to severe vascular risk factors, and it underlies various complex pathophysiological pathways at the metabolic and molecular level that progress and converge toward the development of diabetic cardiomyopathy (DCM). DCM involves several downstream cascades that cause structural and functional alterations of the diabetic heart, such as diastolic dysfunction progressing into sys-tolic dysfunction, cardiomyocyte hypertrophy, myocardial fibrosis, and subsequent heart failure over time. The effects of glucagon-like peptide-1 (GLP-1) analogues and sodium-glucose cotrans-porter-2 (SGLT-2) inhibitors on cardiovascular (CV) outcomes in diabetes have shown promising results, including improved contractile bioenergetics and significant cardiovascular benefits. The purpose of this article is to highlight the various pathophysiological, metabolic, and molecular pathways that contribute to the development of DCM and its significant effects on cardiac morphology and functioning. Additionally, this article will discuss the potential therapies that may be available in the future.
... The miRNA-29 family targets mRNAs of various types of elastin, fibrin, and collagen (including type I and type III collagen) involved in fibrosis, which is a key pathological change related to RIHD in irradiated rats [45] . Cardiac specific miRNA-208 has been proved to be crucial to cardiac hypertrophy, fibrosis, and the expression of β-myosin heavy chain [113] . ...
Radiation-induced heart disease (RIHD) is a potentially fatal clinical complication of chest radiotherapy(RT). RIHD is detrimental to the long-term health of post-RT survivors and limits the dose and intensity of RT required to effectively kill tumor cells. However, the cellular and molecular mechanisms underlying these effects remain largely unknown. MicroRNAs (miRNAs) are highly conserved, non-coding, single-stranded, small molecular RNAs that regulate gene expression and participate in cellular proliferation, apoptosis, differentiation, and disease development. MicroRNA-21 (miRNA-21) has become one of the most intensively studied miRNAs in the fields of cancer and cardiovascular disease in recent years. miRNA-21 plays an important role in RIHD progression. This article reviews the origin and function of miRNA-21 in the cardiovascular system and its role in RIHD pathogenesis. In addition, the potential role of miRNA-21 as a new target for predicting and treating RIHD is also discussed.
... The miRNA-29 family targets mRNAs of various types of elastin, fibrin, and collagen (including type I and type III collagen) involved in fibrosis, which is a key pathological change related to RIHD in irradiated rats [45] . Cardiac specific miRNA-208 has been proved to be crucial to cardiac hypertrophy, fibrosis, and the expression of β-myosin heavy chain [113] . ...
Radiation-induced heart disease (RIHD) is a potentially fatal clinical complication of chest radiotherapy (RT). RIHD is detrimental to the long-term health of post-RT survivors and limits the dose and intensity of RT required to effectively kill tumor cells. However, the cellular and molecular mechanisms underlying these effects remain largely unknown. MicroRNAs (miRNAs) are highly conserved, non-coding, single-stranded, small molecular RNAs that regulate gene expression and participate in cellular proliferation, apoptosis, differentiation, and disease development. MicroRNA-21 (miRNA-21) has become one of the most intensively studied miRNAs in the fields of cancer and cardiovascular disease in recent years. miRNA-21 plays an important role in RIHD progression. This article reviews the origin and function of miRNA-21 in the cardiovascular system and its role in RIHD pathogenesis. In addition, the potential role of miRNA-21 as a new target for predicting and treating RIHD is also discussed. Abstract Despite the increased overall survival rate in patients receiving radiation therapy, its side effects and sequelae have become major obstacles to the patients' quality of life in long-term survival, and radiation-induced heart disease (RIHD) is one of these vital detrimental factors [1]
... Almost 80% of the deaths of diabetic patients occur due to Diabetic heart disease (DHD) and although it starts in the early stages of diabetes, it is not detectable and usually has no symptoms until the last stages of the disease. Therefore, it is important to find early diagnostic methods for this purpose, and miRNAs (miRs) can be studied as biomarkers in the regulation of gene expression and other cellular processes [46][47][48]. ...
... Also, the HIF/HIF pathway by reactive oxygen species can lead to an increase in oxidative stress. Also, the oxidative stress by miRNA and their regulated genes can paradoxically decrease HIF expression after stroke [46]. Under hypoxic conditions, miR-210 is affected by HIF-1α and downregulates PARK7, a redox-responsive cellular protective protein, in diabetic HF patients [50]. ...
Today, we see an increase in death due to cardiovascular diseases all over the world, which has a lot to do with the regulation of oxygen homeostasis. Also, hypoxia-inducing factor 1 (HIF-1) is considered a vital factor in hypoxia and its physiological and pathological changes. HIF-1 is involved in cellular activities, including proliferation, differentiation, and cell death in endothelial cells (ECs) and cardiomyocytes. Similar to HIF-1α, which acts as a protective element against various diseases in the cardiovascular system, the protective role of microRNAs (miRNAs) has also been proved using animal models. The number of miRNAs identified in the regulation of gene expression responsive to hypoxia and the importance of investigating the involvement of the non-coding genome in cardiovascular diseases is increasing, which shows the issue's importance. In this study, the molecular regulation of HIF-1 by miRNAs is considered to improve therapeutic approaches in clinical diagnoses of cardiovascular diseases.
... An increasing number of studies have centered on ncRNAs in DM and its associated complications, suggesting that ncRNAs can interact with insulin [6]. There is also evidence to indicate that ncRNAs may serve as modulators and markers of diabetic cardiovascular disease [7][8][9][10]. This article reviews the role of exosomes and ncRNAs as part of they in the occurrence and development of diabetes and its complications, and discusses the role and prospect of exosomes and ncRNAs as a target for diabetes treatment and in the diagnosis and treatment of diabetes. ...
Diabetes mellitus (DM) is a first-line priority among the problems facing medical science and public health in almost all countries of the world. The main problem of DM is the high incidence of damage to the cardiovascular system, which in turn leads to diseases such as myocardial infarction, stroke, gangrene of the lower extremities, blindness and chronic renal failure. As a result, the study of the molecular genetic mechanisms of the pathogenesis of DM is of critical importance for the development of new diagnostic and therapeutic strategies. Molecular genetic aspects of the etiology and pathogenesis of diabetes mellitus are intensively studied in well-known laboratories around the world. One of the strategies in this direction is to study the role of exosomes in the pathogenesis of DM. Exosomes are microscopic extracellular vesicles with a diameter of 30-100 nm, released into the intercellular space by cells of various tissues and organs. The content of exosomes depends on the cell type and includes mRNA, non-coding RNAs, DNA, and so on. Non-coding RNAs, a group of RNAs with limited transcriptional activity, have been discovered to play a significant role in regulating gene expression through epigenetic and posttranscriptional modulation, such as silencing of messenger RNA. One of the problems of usage exosomes in DM is the identification of the cellular origin of exosomes and the standardization of protocols for molecular genetic studies in clinical laboratories. In addition, the question of the target orientation of exosomes and their targeted activity requires additional study. Solving these and other problems will make it possible to use exosomes for the diagnosis and delivery of drugs directly to target cells in DM. This study presents an analysis of literature data on the role of exosomes and ncRNAs in the development and progression of DM, as well as the prospects for the use of exosomes in clinical practice in this disease.
... MiR-208a was encoded by an intron of the α-cardiac muscle myosin heavy chain gene (MYH6) and expressed only in the heart 20 . Meanwhile, miR-208b which was encoded by an intron of the β-cardiac muscle myosin heavy chain gene (MYH7), expressed in cardiac and skeletal muscles 21 . A previous study has revealed that miR-208 was upregulated in the obese mice induced by high fat diet, whereas the insulin resistance and glucose tolerance were signi cantly improved when miR-208 was down-regulated 22 . ...
Background: Previous studies found that the myocardial function is damaged in obese mice induced by a high-fat diet, with the increased miRNA-208a and decreased IRS-2.
Method: Herein, miR-208a(-/-) knockout and C57BL/6J wild-type mice were divided into the normal diet and high‑fat diet groups, separately. Expressions of p-IRS-2, PI3K, p-AKT, NPPA, AKT, IRS-2, MYH6, MYH7 and Glut4 were determined using immunohistochemical staining. Furthermore, western blotting was performed to identify proteins.
Cardiomyocytes were isolated from neonatal rats, and the cardiomyocytes injury model was induced by PA. CCK-8 was conducted to assess the viability of cardiomyocytes, and the glucose uptake of cardiomyocytes was measured using glucose uptake test.
Result: H&E staining revealed that the degree of hypertrophy and swelling of cardiomyocytes and cardiac fibrosis of miR208a-/- knockout mice in the high-fat diet group was significantly increased. Moreover, high levels of IRS-2, p-AKT, AKT, NPPA ,GLUT4, MYH7 and MYH6 expression in miR208a-/- knockout mice. Therefore, AKT, MYH6, IRS-2, NPPA in miR208a-/- knockout mice of high-fat diet.
In PA-treated cardiomyocytes, the viability was markedly declined and glucose uptake was significantly reduced, while the lipid accumulation and fibrosis were significantly enhanced. Most importantly, the cardiomyocytes injury induced by PA was aggravated in miR-208a-3p upregulated cardiomyocytes, but alleviated in miR-208a-3pdownregulated cardiomyocytes.
Conclusion: Our results indicate that the high expression of miR-208a promote the suppression of IRS-2/PI3K/AKT signaling pathway. Meanwhile, miR-208a-3p contributes to promoting PA-induced cardiomyocyte injury, which may be a biomarker of cardiomyocyte injury in lipotoxic cardiomyopathy.
... An increasing number of studies have focused on ncRNAs in DM and its complications, suggesting that ncRNAs can interact with insulin (18). Evidence also suggests that ncRNAs may serve as modulators and diagnostic markers of diabetic cardiovascular disease (19)(20)(21)(22). ...
More than 10% of the world’s population already suffers from varying degrees of diabetes mellitus (DM), but there is still no cure for the disease. Cardiovascular disease (CVD) is one of the most common and dangerous of the many health complications that can be brought on by DM, and has become the leading cause of death in people with diabetes. While research on DM and associated CVD is advancing, the specific mechanisms of their development are still unclear. Given the threat of DM and CVD to humans, the search for new predictive markers and therapeutic ideas is imminent. Non-coding RNAs (ncRNAs) have been a popular subject of research in recent years. Although they do not encode proteins, they play an important role in living organisms, and they can cause disease when their expression is abnormal. Numerous studies have observed aberrant ncRNAs in patients with DM complications, suggesting that they may play an important role in the development of DM and CVD and could potentially act as biomarkers for diagnosis. There is additional evidence that treatment with existing drugs for DM, such as metformin, alters ncRNA expression levels, suggesting that regulation of ncRNA expression may be a key mechanism in future DM treatment. In this review, we assess the role of ncRNAs in the development of DM and CVD, as well as the evidence for ncRNAs as potential therapeutic targets, and make use of bioinformatics to analyze differential ncRNAs with potential functions in DM.
