The main cause of morbidity and mortality in diabetes mellitus (DM) is cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here, we compared these two models for their effects on cardiac structure, function and transcriptome. Different doses of STZ and diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and nonobese sex- and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR and RNA-seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM affected left ventricular function and myocardial performance differently. T1DM displayed exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis, along with increased cardiac oxidative stress, CM DNA damage and senescence, when compared to T2DM in mice. T1DM and T2DM affected the whole cardiac transcriptome differently. In conclusion, the STZ-induced T1DM and T2DM mouse models showed significant differences in cardiac remodeling, function and the whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.

Vascular calcification (VC) is a biological phenomenon characterized by an accumulation of calcium and phosphate deposits within the walls of blood vessels causing the loss of elasticity of the arterial walls. VC plays a crucial role in the incidence and progression of chronic kidney disease (CKD), leading to a significant increase in cardiovascular mortality in these patients. Different conditions such as age, sex, dyslipidemia, diabetes, and hypertension are the main risk factors in patients affected by chronic kidney disease. However, VC may occur earlier and faster in these patients if it is associated with new or non-traditional risk factors such as oxidative stress, anemia, and inflammation. In chronic kidney disease, several pathophysiological processes contribute to vascular calcifications, including osteochondrogenic differentiation of vascular cells, hyperphosphatemia and hypercalcemia, and the loss of specific vascular calcification inhibitors including pyrophosphate, fetuin-A, osteoprotegerin, and matrix GLA protein. In this review we discuss the main traditional and non-traditional risk factors that can promote VC in patients with kidney disease. In addition, we provide an overview of the main pathogenetic mechanisms responsible for VC that may be crucial to identify new prevention strategies and possible new therapeutic approaches to reduce cardiovascular risk in patients with kidney disease.

Ischemic stroke is among the leading causes of morbidity, disability, and mortality worldwide. Despite the recent progress in the management of acute ischemic stroke, timely intervention still represents a challenge. Hence, strategies to counteract ischemic brain injury during and around the acute event are still lacking, also due to the limited knowledge of the underlying mechanisms. Despite the increasing understanding of the complex pathophysiology underlying ischemic brain injury, some relevant pieces of information are still required, particularly regarding the fine modulation of biological processes. In this context, there is emerging evidence that the modulation of circular RNAs, a class of highly conserved non-coding RNA with a closed-loop structure, are involved in pathophysiological processes behind ischemic stroke, unveiling a number of potential therapeutic targets and possible clinical biomarkers. This paper aims to provide a comprehensive overview of experimental studies on the role of circular RNAs in ischemic stroke.

Cardiomyopathies are the structural and functional disorders of the myocardium. Etiopathogenesis is complex and involves an interplay of genetic, environmental, and lifestyle factors eventually leading to myocardial abnormalities. It is known that non-coding (Nc) RNAs, including micro (mi)-RNAs and long non-coding (lnc) RNAs, play a crucial role in regulating gene expression. Several studies have explored the role of miRNAs in the development of various pathologies, including heart diseases. In this review, we analyzed various patterns of ncRNAs expressed in the most common cardiomyopathies: dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic cardiomyopathy. Understanding the role of different ncRNAs implicated in cardiomyopathic processes may contribute to the identification of potential therapeutic targets and novel risk stratification models based on gene expression. The analysis of ncRNAs may also be helpful to unveil the molecular mechanisms subtended to these diseases.

Cardiovascular calcification is a multifactorial and complex process involving an array of molecular mechanisms eventually leading to calcium deposition within the arterial walls. This process increases arterial stiffness, decreases elasticity, influences shear stress events and is related to an increased risk of morbidity and mortality associated with cardiovascular disease. In numerous in vivo and in vitro models, warfarin therapy has been shown to cause vascular calcification in the arterial wall. However, the exact mechanisms of calcification formation with warfarin remain largely unknown, although several molecular pathways have been identified. Circulating miRNA have been evaluated as biomarkers for a wide range of cardiovascular diseases, but their exact role in cardiovascular calcification is limited. This review aims to describe the current state-of-the-art research on the impact of warfarin treatment on the development of vascular calcification and to highlight potential molecular targets, including microRNA, within the implicated pathways.

Background: Three-dimensional cell culture systems hold great promise for bridging the gap between in vitro cell-based model systems and small animal models to study tissue biology and disease. Among 3D cell culture systems, stem-cell-derived spheroids have attracted significant interest as a strategy to better mimic in vivo conditions. Cardiac stem cell/progenitor (CSC)-derived spheroids (CSs) provide a relevant platform for cardiac regeneration. Methods: We compared three different cell culture scaffold-free systems, (i) ultra-low attachment plates, (ii) hanging drops (both requiring a 2D/3D switch), and (iii) agarose micro-molds (entirely 3D), for CSC-derived CS formation and their cardiomyocyte commitment in vitro. Results: The switch from a 2D to a 3D culture microenvironment per se guides cell plasticity and myogenic differentiation within CS and is necessary for robust cardiomyocyte differentiation. On the contrary, 2D monolayer CSC cultures show a significant reduced cardiomyocyte differentiation potential compared to 3D CS culture. Forced aggregation into spheroids using hanging drop improves CS myogenic differentiation when compared to ultra-low attachment plates. Performing CS formation and myogenic differentiation exclusively in 3D culture using agarose micro-molds maximizes the cardiomyocyte yield. Conclusions: A 3D culture system instructs CS myogenic differentiation, thus representing a valid model that can be used to study adult cardiac regenerative biology.