Small but smart--microRNAs in the centre of inflammatory processes during cardiovascular diseases, the metabolic syndrome, and ageing

With a progressively growing elderly population, ageing-associated pathologies such as cardiovascular diseases are becoming an increasing economic, social, and personal burden for Western societies. Interestingly, all ageing-associated diseases share a common denominator: inflammation. Recently, microRNAs were shown to be implicated in the full range of processes of ageing, inflammation, and cardiovascular diseases. This review focuses on their role in cardiovascular diseases with emphasis on their implication in the inflammatory processes that accompany heart failure, atherosclerosis, coronary artery disease, and finally obesity and diabetes as components of the ageing-associated metabolic syndrome.     

Obesity and type-2 diabetes as inducers of premature cellular senescence and ageing

Cellular senescence is now considered as a major mechanism in the development and progression of various diseases and this may include metabolic diseases such as obesity and type-2 diabetes. The presence of obesity and diabetes is a major risk factor in the development of additional health conditions, such as cardiovascular disease, kidney disease and cancer. Since senescent cells can drive disease development, obesity and diabetes can potentially create an environment that accelerates cell senescence within other tissues of the body. This can consequently manifest as age-related biological impairments and secondary diseases. Cell senescence in cell types linked with obesity and diabetes, namely adipocytes and pancreatic beta cells will be explored, followed by a discussion on the role of obesity and diabetes in accelerating ageing through induction of premature cell senescence mediated by high glucose levels and oxidised low-density lipoproteins. Particular emphasis will be placed on accelerated cell senescence in endothelial progenitor cells, endothelial cells and vascular smooth muscle cells with relation to cardiovascular disease and proximal tubular cells with relation to kidney disease. A summary of the potential strategies for therapeutically targeting senescent cells for improving health is also presented.     

microRNA与脂肪组织慢性低度炎性反应

脂肪组织慢性低度炎性反应是肥胖、2型糖尿病、高血压、心血管疾病等代谢性疾病的中心环节.研究脂肪组织慢性低度炎性反应的精确调控过程,对于预防和治疗肥胖及相关疾病有重要意义.microRNA是一类非编码RNA,具有调节基因表达的功能.研究显示,microRNA对脂肪组织巨噬细胞、经典炎性反应信号通路及炎性因子、抗炎因子等具有调控作用.     

脂肪因子与慢性心力衰竭研究进展

慢性心力衰竭的发病率和病死率高。肥胖、高血压和糖尿病等为慢性心力衰竭的传统危险因素,但近期研究表明发现肥胖的慢性心力衰竭患者预后较好,这一现象被人称为“肥胖悖论”。脂肪组织目前被认为是一种内分泌组织,分泌的多种脂肪因子可调控多种心血管功能。现综述可影响心血管功能的脂肪因子。     

Obesity, diabetes, and associated risk factors

Optional statement The prevalence of obesity has increased in the past 10 years. Recent studies have associated obesity with other cardiovascular risk factors, and an increased risk of diabetes and cardiovascular death. Patients with obesity should undergo a global evaluation cardiovascular risk, including measurement of abdominal waist circumference, assessment of standard cardiovascular risk factors, screening for dyslipidemia, abnormal glucose metabolism, and hypertension. Recommendations for dietary modification should be tailored to the patient’s associated medical conditions, such as diabetes, dyslipidemia, and hypertension, and all patients should be instructed on the importance of monitoring caloric intake. For patients who can engage in regular physical activity, we recommend a minimum regimen of 150 min/wk of moderate intensity exercise, such as brisk walking. Use of pharmacotherapy for obesity can be considered when efforts at therapeutic lifestyle modification have been ineffective, but patients must be carefully screened because many agents have potential side effects. Surgical approaches for obesity have also been demonstrated to be effective in achieving and sustaining weight loss and improving markers of cardiovascular risk and should be considered in patients who are refractory to therapeutic lifestyle modification. All diabetic patients should be treated comprehensively to reduce other comorbid conditions, including hypertension and dyslipidemia. Hypoglycemic therapy should be initiated when efforts to reduce hyperglycemia to target thresholds fail.     

GLP-1/glucagon receptor co-agonism for treatment of obesity

Over a relatively short period, obesity and type 2 diabetes have come to represent a large medical and economic burden to global societies. The epidemic rise in the prevalence of obesity has metabolic consequences and is paralleled by an increased occurrence of other diseases, such as diabetes, cancer and cardiovascular complications. Together, obesity and type 2 diabetes constitute one of the more preventable causes of premature death and the identification of novel, safe and effective anti-obesity drugs is of utmost importance. Pharmacological attempts to treat obesity have had limited success, with notable adverse effects, rendering bariatric surgery as the only current therapy for substantially improving body weight. Novel unimolecular, multifunctional peptides have emerged as one of the most promising medicinal approaches to enhance metabolic efficacy and restore normal body weight. In this review, we will mainly focus on the discovery and translational relevance of dual agonists that pharmacologically function at the receptors for glucagon and glucagon-like peptide-1. Such peptides have advanced to clinical evaluation and inspired the pursuit of multiple related approaches to achieving polypharmacy within single molecules.     

Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review

There are controversies regarding the association of visfatin with overweight/obesity, type 2 diabetes mellitus, insulin resistance (IR), metabolic syndrome and cardiovascular disease in published articles. A meta-analysis was performed to identify the significance of visfatin in these diseases. We searched for relevant articles in Pubmed, Scopus and SCIE. A total of 1035 articles were surveyed and 46 articles were identified, with 14 reports reporting more than one of our investigated diseases. A total of 13 (n = 644), 19 (n = 2405), 20 (n = 2249), 5 (n = 527) and 5 (n = 851) articles/(participants) were included in each meta-analysis regarding the association of visfatin and overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases, respectively. Plasma visfatin concentrations were increased in participants diagnosed with overweight/obesity, type 2 diabetes mellitus, metabolic syndrome and cardiovascular diseases, with pooled log odds ratios of 1.164 [95% confidence interval (CI): 0.348 to 1.981, p = 0.005], 1.981 (95% CI: 1.377 to 2.584, p < 0.001), 1.094 (95% CI: 0.678 to 1.511, p < 0.001), and 2.902 (95% CI: 0.924 to 4.879, p < 0.005), respectively. The circulating visfatin level was positively associated with insulin resistance, with a Fisher's z of 0.089 (95% CI: 0.013 to 0.165, p = 0.022). No single study was found to affect the overall result of each analysis by sensitivity testing. No publication bias was found by the Egger test. Our study suggests that the use of visfatin may be promising for predicting obesity, diabetes status, insulin resistance, metabolic syndrome and cardiovascular disease.     

Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism

Obesity is becoming a global epidemic in both children and adults. It is associated with numerous comorbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, obesity is an independent risk factor for CVD, and CVD risks have also been documented in obese children. Obesity is associated with an increased risk of morbidity and mortality as well as reduced life expectancy. Health service use and medical costs associated with obesity and related diseases have risen dramatically and are expected to continue to rise. Besides an altered metabolic profile, a variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amounts, even in the absence of comorbidities. Hence, obesity may affect the heart through its influence on known risk factors such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, obstructive sleep apnea/hypoventilation, and the prothrombotic state, in addition to as-yet-unrecognized mechanisms. On the whole, overweight and obesity predispose to or are associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death because of their impact on the cardiovascular system. The pathophysiology of these entities that are linked to obesity will be discussed. However, the cardiovascular clinical evaluation of obese patients may be limited because of the morphology of the individual. In this statement, we review the available evidence of the impact of obesity on CVD with emphasis on the evaluation of cardiac structure and function in obese patients and the effect of weight loss on the cardiovascular system.     

Genetic Epidemiology of Type 2 Diabetes and Cardiovascular Diseases in Africa

The burdens of type 2 diabetes (T2D) and cardiovascular diseases (CVD) are increasing in Africa. T2D and CVD are the result of the complex interaction between inherited characteristics, lifestyle, and environmental factors. The epidemic of obesity is largely behind the exploding global incidence of T2D. However, not all obese individuals develop diabetes and positive family history is a powerful risk factor for diabetes and CVD. Recent implementations of high throughput genotyping and sequencing approaches have advanced our understanding of the genetic basis of diabetes and CVD by identifying several genomic loci that were not previously linked to the pathobiology of these diseases. However, African populations have not been adequately represented in these global genomic efforts. Here, we summarize the state of knowledge of the genetic epidemiology of T2D and CVD in Africa and highlight new genomic initiatives that promise to inform disease etiology, public health and clinical medicine in Africa.     

Following in the Footsteps of the North Karelia Project: Prevention of Type 2 Diabetes

The prevalence as well as actual number of people with type 2 diabetes has been increasing in Finland during the past decades, in parallel with an increase in overweight and obesity. Besides obesity, population aging is among the main drivers of increasing numbers of diabetic patients. Type 2 diabetes brings along complications, most importantly cardiovascular diseases, and increasing type 2 diabetes prevalence has also been suggested to lead to a new upward turn in cardiovascular diseases. Therefore, it is important to implement activities to prevent type 2 diabetes. We present the trial evidence for the prevention of type 2 diabetes with emphasis on the Finnish Diabetes Prevention Study findings. Furthermore, we discuss the practical implementation of screening of individuals for high type 2 diabetes risk and prevention of type 2 diabetes in Finland at the population level and describe how they have contributed to European level initiatives.     

Chronic inflammation links cardiovascular, metabolic and renal diseases

Chronic inflammation appears to underlie most, if not all, the chronic diseases of today, including cardiovascular disease, type 2 diabetes, chronic kidney disease, Alzheimer's disease and cancer. We have demonstrated that obesity induces chronic local inflammation in adipose tissue. We also found that chronic inflammation is crucially involved in the development of heart failure and chronic kidney disease. In this article, I review recent findings reported by my group and others regarding the mechanisms underlying the chronic inflammatory processes commonly observed in adipose tissue, heart and kidney. I then discuss the key features of the chronic inflammation seen in chronic diseases.     

Cardiovascular physiology at the bench for application in the clinic

Our research focuses on microphysiological aspects of the cardiovascular system, with an emphasis on what is occurring in heart tissues, to learn more about how various diseases arise and how they can be avoided or cured. These diseases include atherosclerosis, diabetes, myocardial infarction, obesity and ischemia/reperfusion (I/R). We use animal models, particularly mice, to aid us in these studies. A key feature of our work centers on dissection of coronary arterioles and examining their functionality using drugs, electrophysiology, fluoroscopy, genomics, proteomics, and standard chemical analyses to determine their physiological status, and compare it with other treated animals. My laboratory is focusing on anti-inflammatory and antioxidative stress therapeutic effects, the roles of sodium salicylate, exercise and resveratrol in type 2 diabetes, I/R injury, obesity, and atherosclerosis. Recently, we began investigations of the effects of stem cells and gastric bypass surgery on vascular dysfunction in obesity and diabetes. Our work identifies how diet, exercise, surgical interventions and drugs can be considered to combat these diseases in a clinical setting.     

脂氧素与代谢性疾病的研究进展

脂氧素(LX)是体内重要的内源性脂质抗炎介质,来源于花生四烯酸,具有抗炎和促炎症消退的作用。近年来, LX在糖尿病、肥胖、心血管疾病等代谢性疾病中的作用引起广泛关注。为此,本文就LX的生物学作用,以及其在代谢性疾病中的研究进展做一简要综述。     

Metabolomics and Atherosclerosis

Metabolites reflect the dynamic processes underlying cellular homeostasis. Recent advances in analytical chemistry and molecular biology have set the stage for metabolite profiling to help us understand complex molecular processes and physiology. Metabolomics is the comparative analysis of metabolite flux and how it relates to biological phenotypes. As an intermediate phenotype, metabolite signatures capture a unique aspect of cellular dynamics that is not typically interrogated, providing a distinct perspective on cellular homeostasis. To date, there have been only a few metabolomics studies investigating cardiovascular diseases. In this review, we explore the principles of metabolomics and how it can provide further insight into the mechanisms of cardiovascular physiology and ultimately lead to improved diagnostic and therapeutic options for patients with cardiovascular disease.     

Expression of microRNAs: potential molecular link between obesity,diabetes and cancer

Clinicians are routinely challenged in their management of cancer patients because of the complexities of obesity and diabetes that are often found as comorbid conditions. Although attention has been given to optimizing treatment planning for these patients, less attention has been given to manage their obesity and diabetes. This suggests that newer, comprehensive approaches must be developed for the treatment of cancer patients as a ‘whole’ rather than as a single disease. While the specific pathologies of each are unique, years of research have indicated intimate molecular links between these chronic diseases. The contribution of sedentary lifestyles and poor dietary habits is recognized; however, the precise molecular links are still not well‐explored. In addition, emerging evidence suggests the important role of microRNAs (miRNAs) in the development and progression of several diseases, yet their roles in linking obesity, diabetes and cancer are only now beginning to be recognized. It is hoped that miRNAs will serve as novel biomarkers and molecular targets for cancer therapy in patients with comorbid conditions. In this review, we discuss the current understanding of the pathobiology of obesity, diabetes and cancer, and document molecular roles of miRNAs linking cancer with obesity and diabetes.     

Intra-abdominal adiposity,inflammation, and cardiovascular risk: New insight into global cardiometabolic risk

Increasing evidence supports the role of adipose tissue in the development of a systemic inflammatory state, which contributes to obesity-associated vasculopathy and cardiovascular risk. In addition to storing calories as triglycerides, adipocytes secrete a large variety of proteins, including cytokines, chemokines, and hormone-like factors (eg, leptin, adiponectin, resistin). This production of pro chemokines by adipose tissue is of particular interest, because their local secretion by perivascular adipose depots may provide a new mechanistic link between obesity and its associated vascular complications. Insulin resistance, in subjects with or without diabetes, is frequently associated with obesity, particularly with an excess of intra-abdominal fat. Recently, the endocannabinoid system, among others, has been shown to be involved in the pathophysiology of visceral obesity and global cardiometabolic risk, as represented by the overall risk of developing type 2 diabetes or cardiovascular diseases.     

Diabetes,obesity and gut microbiota

The gut microbiota composition has been associated with several hallmarks of metabolic syndrome (e.g., obesity, type 2 diabetes, cardiovascular diseases, and non-alcoholic steatohepatitis). Growing evidence suggests that gut microbes contribute to the onset of the low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. Recently, enteroendocrine cells and the endocannabinoid system have been shown to control gut permeability and metabolic endotoxaemia. Moreover, targeted nutritional interventions using non-digestible carbohydrates with prebiotic properties have shown promising results in pre-clinical studies in this context, although human intervention studies warrant further investigations. Thus, in this review, we discuss putative mechanisms linking gut microbiota and type 2 diabetes. These data underline the advantage of investigating and changing the gut microbiota as a therapeutic target in the context of obesity and type 2 diabetes.     

Intra-abdominal adiposity, inflammation, and cardiovascular risk: New insight in the global cardiometabolic risk

Increasing evidence supports the role of adipose tissue in the development of a systemic inflammatory state, which contributes to obesity-associated vasculpathy and cardiovascular risk. In addition to storing calories as triglycerides, adipocytes secrete a large variety of proteins, including cytokines, chemokines, and hormone-like factors (eg, leptin, adiponectin, resistin). This production of pro chemokines by adipose tissue is of particular interest, because their local secretion by perivascular adipose depots may provide a new mechanistic link between obesity and its associated vascular complications. Insulin resistance, in subjects with or without diabetes, is frequently associated with obesity, particularly with an excess of intra-abdominal fat. Recently, the endocannabinoid system, among others, has been shown to be involved in the pathophysiology of visceral obesity and global cardiometabolic risk, as represented by the overall risk of developing type 2 diabetes or cardiovascular diseases.     

Obesity,diabetes, and coronary risk in women

The latter half of the twentieth century has witnessed rapid advances in cardiovascular epidemiology and medicine. Concurrently, secular trends in lifestyle practices and general improvements in standards of living have resulted in several alarming trends for cardiovascular disease prevention and health promotion. The adoption of unhealthy dietary patterns, growing socio-economic and racial disparities in chronic disease prevalence, low levels of physical activity, and other as yet unidentified genetic and environmental determinants have led to burgeoning rates of both pediatric and adult obesity and diabetes mellitus. Women appear to be at particular risk as the gender advantage for coronary heart disease (CHD) is counterbalanced by an increased incidence of obesity and diabetes. In order to further examine these complex associations, we review the available epidemiological data regarding the impact of obesity and diabetes on cardiovascular health in women.     

Early intervention and intensive management of patients with diabetes,cardiorenal, and metabolic diseases

Increasing rates of obesity and diabetes have driven corresponding increases in related cardiorenal and metabolic diseases. In many patients, these conditions occur together, further increasing morbidity and mortality risks to the individual. Yet all too often, the risk factors for these disorders are not addressed promptly in clinical practice, leading to irreversible pathologic progression. To address this gap, we convened a Task Force of experts in cardiology, nephrology, endocrinology, and primary care to develop recommendations for early identification and intervention in obesity, diabetes, and other cardiorenal and metabolic diseases. The recommendations include screening and diagnosis, early interventions with lifestyle, and when and how to implement medical therapies. These recommendations are organized into primary and secondary prevention along the continuum from obesity through the metabolic syndrome, prediabetes, diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), atherosclerotic cardiovascular disease (ASCVD) and atrial fibrillation, chronic kidney disease (CKD), and heart failure (HF). The goal of early and intensive intervention is primary prevention of comorbidities or secondary prevention to decrease further worsening of disease and reduce morbidity and mortality. These efforts will reduce clinical inertia and may improve patients' well-being and adherence.