Background:Statin use is frequently associated with muscle-related symptoms. Coenzyme Q10 supplementation has yielded conflicting results in decreasing statin myopathy. Herein, we tested whether coenzyme Q10 supplementation could decrease statin-asso...

In diabetic patients, cardiomyopathy is an important cause of heart failure, but its pathophysiology has not been completely understood thus far. Myocardial hypertrophy and diastolic dysfunction have been considered the hallmarks of diabetic cardiomyopathy (DCM), while systolic function is affected in the latter stages of the disease. In this article we propose the potential pathophysiological mechanisms responsible for myocardial hypertrophy and increased myocardial stiffness leading to diastolic dysfunction in this specific entity. According to our model, increased myocardial stiffness results from both cellular and extracellular matrix stiffness as well as cell–matrix interactions. Increased intrinsic cardiomyocyte stiffness is probably the most important contributor to myocardial stiffness. It results from the impairment in cardiomyocyte cytoskeleton. Several other mechanisms, specifically affected by diabetes, seem to also be significantly involved in myocardial stiffening, i.e., impairment in the myocardial nitric oxide (NO) pathway, coronary microvascular dysfunction, increased inflammation and oxidative stress, and myocardial sodium glucose cotransporter-2 (SGLT-2)-mediated effects. Better understanding of the complex pathophysiology of DCM suggests the possible value of drugs targeting the listed mechanisms. Antidiabetic drugs, NO-stimulating agents, anti-inflammatory agents, and SGLT-2 inhibitors are emerging as potential treatment options for DCM.

The incidence of aging-related disorders may be decreased through strategies influencing the expression of longevity genes. Although numerous approaches have been suggested, no effective, safe, and easily applicable approach is yet available. Efficacy of low-dose fluvastatin and valsartan, separately or in combination, on the expression of the longevity genes in middle-aged males, was assessed. Stored blood samples from 130 apparently healthy middle-aged males treated with fluvastatin (10 mg daily), valsartan (20 mg daily), fluvastatin-valsartan combination (10 and 20 mg, respectively), and placebo (control) were analyzed. They were taken before and after 30 days of treatment and, additionally, five months after treatment discontinuation. The expression of the following longevity genes was assessed: SIRT1, PRKAA, KLOTHO, NFE2L2, mTOR, and NF-κB. Treatment with fluvastatin and valsartan in combination significantly increased the expression of SIRT1 (1.8-fold; p < 0.0001), PRKAA (1.5-fold; p = 0.262) and KLOTHO (1.7-fold; p < 0.0001), but not NFE2L2, mTOR and NF-κB. Both fluvastatin and valsartan alone significantly, but to a lesser extent, increased the expression of SIRT1, and did not influence the expression of other genes. Five months after treatment discontinuation, genes expression decreased to the basal levels. In addition, analysis with previously obtained results revealed significant correlation between SIRT1 and both increased telomerase activity and improved arterial wall characteristics. We showed that low-dose fluvastatin and valsartan, separately and in combination, substantially increase expression of SIRT1, PRKAA, and KLOTHO genes, which may be attributed to their so far unreported pleiotropic beneficial effects. This approach could be used for prevention of ageing (and longevity genes)–related disorders.

Cellular senescence is a complex, dynamic process consisting of the irreversible arrest of growth and gradual deterioration of cellular function. Endothelial senescence affects the cell’s ability to repair itself, which is essential for maintaining vascular integrity and leads to the development of endothelial dysfunction, which has an important role in the pathogenesis of cardiovascular diseases. Senescent endothelial cells develop a particular, senescence-associated secretory phenotype (SASP) that detrimentally affects both surrounding and distant endothelial cells, thereby facilitating the ageing process and development of age-related disorders. Recent studies highlight the role of endothelial senescence and its dysfunction in the pathophysiology of several age-related diseases. MicroRNAs are small noncoding RNAs that have an important role in the regulation of gene expression at the posttranscriptional level. Recently, it has been discovered that miRNAs could importantly contribute to endothelial cell senescence. Overall, the research focus has been shifting to new potential mechanisms and targets to understand and prevent the structural and functional changes in ageing senescent endothelial cells in order to prevent the development and limit the progression of the wide spectrum of age-related diseases. The aim of this review is to provide some insight into the most important pathways involved in the modulation of endothelial senescence and to reveal the specific roles of several miRNAs involved in this complex process. Better understanding of miRNA’s role in endothelial senescence could lead to new approaches for prevention and possibly also for the treatment of endothelial cells ageing and associated age-related diseases.