1,721,200 research outputs found
Human-Induced pluripotent stem cells: In quest of clinical applications
No full textIn the field of regenerative medicine, the development of induced pluripotent stem (iPS) cells may represent a potential strategy to overcome the limitations of human embryonic stem cells (ESCs). iPS cells have the potential to mimic human disease, since they carry the genome of the donor. Hypothetically, with iPS cell technology it is possible to screen patients for a genetic cause of disease (genetic mutation), develop cell lines, reprogram them back to iPS cells, finally differentiate them into one or more cell types that develop the disease. Although the creation of multiple lineages with iPS cells can seem limitless, a number of challenges need to be addressed in order to effectively use these cell lines for disease modeling. These include the low efficiency of iPS cell generation without genetic alterations, the possibility of tumor formation in vivo, the random integration of retroviral-based delivery vectors into the genome, and unregulated growth of the remaining cells that are partially reprogrammed and refractory to differentiation. The establishment of protein or RNA-based reprogramming strategies will help generate human iPS cells without permanent genetic alterations. Finally, direct reprogramming strategies can provide rapid production of models of human "diseases in a dish", without first passing the cells through a pluripotent state, so avoiding the challenges of time-consumming and labor-intensive iPS cell line generation. This review will overview methods to develop iPS cells, current strategies for direct reprogramming, and main applications of iPS cells as human disease model, focusing on human cardiovascular diseases, with the aim to be a potential information resource for biomedical scientists and clinicians who exploit or intend to exploit iPS cell technology in a range of applications. © Springer Science+Business Media, LLC 2011
Vascular rejuvenation: A new therapeutic target?
No full textAgeing is a major risk factor for cardiovascular disease.1 With the occurrence of cellular ageing, favoured by the exposure to cardiovascular risk factors, comorbidities, and various stressors, such as bouts of ischaemia and/or ischaemia–reperfusion, the function and cross-talk of cardiac stromal cells (CSCs) and vascular and parenchymal cells, including cardiomyocytes, is diminished, hampering their cardioprotective potential.2
Ageing is also an important determinant of metabolic disorders, including obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome.1 Older men and women tend to have worsened glycaemia-related parameters, i.e. fasting and 2-h plasma glucose and HbA1c concentrations, than their younger counterparts
Exploring the mechanisms of action of gliflozines in heart failure and possible implications in pulmonary hypertension
No full textAlthough results from two major trials trials have shown a clear benefit of gliflozines in the management of heart failure (HF) irrespective of diabetes status, the mechanism of cardiac benefits remains incompletely understood. Gliflozines have an osmotic diuretic effect that differs from that of other diuretic classes, resulting in greater electrolyte-free water clearance, and clinical studies have shown that intravascular volume depletion is rare and occurs at similar frequency in the gliflozines and placebo groups. As a consequence of the negligible effects on the blood volume and body's fluid balance compared to diuretics, gliflozines may limit the reflex neurohumoral stimulation and activation of renin-angiotensin-aldosterone system (RAAS). Since neurohormonal and RAAS activation in patients with HF reduced or ejection fraction (HFrEF and HFpEF) also leads to systemic and pulmonary arterial stiffening, pulmonary hypertension (PH) and PH-related right ventricular failure, gliflozines may lead to a mitigation of systemic and pulmonary arterial stiffening, which in turn can reduce the degree of PH associated with HFrEF or HFpEF, can improve the ventricular arterial coupling and can reduce the overload of the left and right ventricle, improving their function. The current review discusses the latest findings regarding the effects of SGLT2 inhibitors on heart failure with focus also on pulmonary hypertension, discussing the molecular mechanisms involved
Insights into gene therapy for critical limb ischemia: The devil is in the details
No full textPatients with critical limb ischemia (CLI) without potential for revascularization are currently without alternate therapies. Several gene therapy trials have tested angiogenesis factors, hepatic growth factor, vascular endothelial growth factor, and basic fibroblast growth factor, in rescuing CLI patients from amputation and mortality, and for improved quality of life including decreased pain, improved healing, and blood flow. Trial results have been variable, with HGF gene therapy being the most successful. New studies examining each of these angiogenic factors provide insights that will be useful for the design of effective therapeutic strategies. © 2012 Elsevier Inc
Novel strategies in the treatment of pulmonary arterial hypertension
No full textPulmonary arterial hypertension (PAH) is a pathophysiological condition characterized by increased pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies confirmed the key role of endothelin (ET)-1 in the vasoconstriction and remodeling of pulmonary microcirculation during PAH. In responders patients, classical treatments for PAH are prostanoids, phosphodiesterase (PDE)-5 inhibitors and endothelin receptor antagonists (ERAs), which target prostaglandin I2, nitric oxide and endothelin pathways, respectively. Randomised, placebo-controlled trials have shown that ERAs improves haemodynamic parameters of the pulmonary circulation, functional capacity and clinical outcome in patients affected by PAH. Here, we will review the definition, classification and pathophysiology of PH. Furthermore, we will provide an up-to-date overview of currently recommended diagnostic and therapeutic work-up in PAH
Sodium-hydrogen exchangers (NHE) in human cardiovascular diseases: interfering strategies and their therapeutic applications.
No full textCytochromes CYP1A1 and CYP1B1: new pieces in the puzzle to understand the biomechanical paradigm of atherosclerosis
No full textThis is a correction to: Cardiovascular Research, Volume 81, Issue 4, 1 March 2009, Pages 669–677, https://doi.org/10.1093/cvr/cvn36
- …
