Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells has a neutral effect on obesity-induced diabetic cardiomyopathy

Obesity is a major global health issue. Obese patients develop metabolic syndrome, which is a cluster of clinical features characterized by insulin resistance and dyslipidemia. Its cardiac manifestation, diabetic cardiomyopathy, leads to heart failure. Bone marrow-derived multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSC) are envisioned as a therapeutic tool not only for cardiovascular diseases but also for other degenerative conditions. Our aim was to evaluate whether the intravenous administration of MSC modifies cardiac dysfunction in obese mice. To this end, C57BL/6 mice were fed a regular (normal) or high-fat diet (obese). Obese animals received the vehicle (obese), a single dose (obese + 1x MSC) or three doses (obese + 3x MSC) of 0.5x10(6) syngeneic MSC. Two to three months following MSC administration, cardiac function was assessed by cardiac catheterization, at basal condition and after a pharmacological stress. Compared to normal mice, obese mice presented hyperglycemia, hyperinsulinemia, hypercholesterolemia and cardiac dysfunction after stress condition. Exogenous MSC neither improved nor impaired this cardiac dysfunction. Thus, intravenous administration of MSC has neutral effect on obesity-induced diabetic cardiomyopath

Subclinical detection of diabetic cardiomyopathy with micrornas: challenges and perspectives

The prevalence of cardiac diabetic diseases has been increased around the world, being the most common cause of death and disability among diabetic patients. In particular, diabetic cardiomyopathy is characterized with a diastolic dysfunction and cardiac remodelling without signs of hypertension and coronary artery diseases. In an early stage, it is an asymptomatic disease; however, clinical studies demonstrate that diabetic myocardia are more vulnerable to injury derived by acute myocardial infarct and are the worst prognosis for rehabilitation. Currently, biochemical and imaging diagnostic methods are unable to detect subclinical manifestation of the disease (prior to diastolic dysfunction). In this review, we elaborately discuss the current scientific evidences to propose circulating microRNAs as promising biomarkers for early detection of diabetic cardiomyopathy and, then, to identify patients at high risk of diabetic cardiomyopathy development. Moreover, here we summarise the research strategies to identify miRNAs as potential biomarkers, present limitations, challenges, and future perspectives

Subclinical detection of diabetic cardiomyopathy with micrornas: challenges and perspectives

The prevalence of cardiac diabetic diseases has been increased around the world, being the most common cause of death and disability among diabetic patients. In particular, diabetic cardiomyopathy is characterized with a diastolic dysfunction and cardiac remodelling without signs of hypertension and coronary artery diseases. In an early stage, it is an asymptomatic disease; however, clinical studies demonstrate that diabetic myocardia are more vulnerable to injury derived by acute myocardial infarct and are the worst prognosis for rehabilitation. Currently, biochemical and imaging diagnostic methods are unable to detect subclinical manifestation of the disease (prior to diastolic dysfunction). In this review, we elaborately discuss the current scientific evidences to propose circulating microRNAs as promising biomarkers for early detection of diabetic cardiomyopathy and, then, to identify patients at high risk of diabetic cardiomyopathy development. Moreover, here we summarise the research strategies to identify miRNAs as potential biomarkers, present limitations, challenges, and future perspectives

Subclinical Detection of Diabetic Cardiomyopathy with MicroRNAs: Challenges and Perspectives

The prevalence of cardiac diabetic diseases has been increased around the world, being the most common cause of death and disability among diabetic patients. In particular, diabetic cardiomyopathy is characterized with a diastolic dysfunction and cardiac remodelling without signs of hypertension and coronary artery diseases. In an early stage, it is an asymptomatic disease; however, clinical studies demonstrate that diabetic myocardia are more vulnerable to injury derived by acute myocardial infarct and are the worst prognosis for rehabilitation. Currently, biochemical and imaging diagnostic methods are unable to detect subclinical manifestation of the disease (prior to diastolic dysfunction). In this review, we elaborately discuss the current scientific evidences to propose circulating microRNAs as promising biomarkers for early detection of diabetic cardiomyopathy and, then, to identify patients at high risk of diabetic cardiomyopathy development. Moreover, here we summarise the research strategies to identify miRNAs as potential biomarkers, present limitations, challenges, and future perspectives

Blood pressure parameters of normal and obese mice.

<p>(A) Systolic blood pressure (SBP) was determined with sphygmomanometer (non-invasive determination) up to 12 months. (B) Mean arterial pressure was determined with cardiac catheterization (invasive determination) at eight and 16 months. n = 5–6. Mean ± SEM.</p

Collagen type I and collagen type III content in myocardium of normal and obese mice.

<p>(A and C) Representative immunoblots at eight and 16 months. Tubulin was detected as a loading control. (B and D) Densitometric measurements (arbitrary units). n = 7–8. p<0.05 vs. normal mice (Student test). COL I: collagen type I, COL III: collagen type III.</p

Biochemical Markers Related to Metabolic Syndrome.

<p>Results are expressed in mean ± SEM. Student test vs. normal mice,</p>*<p>p<0.05,</p>**<p>p<0.01, n = 10.</p

Vascular reactivity of normal and obese mice.

<p>The aortic ring of normal and obese mice was exposed to different vasoactive agents at 16 months. (A) Vasoconstriction by norepinephrine. (B) Vasorelaxation by acetylcoline. (C) Vasorelaxation by sodium nitroprusside. n = 4. Mean ± SEM, p<0.05 vs. normal mice (Two-way ANOVA test).</p