Regenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements

From the first success in cultivation of cells in vitro, it became clear that developing cell and/or tissue specific cultures would open a myriad of new opportunities for medical research. Expertise in various in vitro models has been developing over decades, so nowadays we benefit from highly specific in vitro systems imitating every organ of the human body. Moreover, obtaining sufficient number of standardized cells allows for cell transplantation approach with the goal of improving the regeneration of injured/disease affected tissue. However, different cell types bring different needs and place various types of hurdles on the path of regenerative neurology and regenerative cardiology. In this review, written by European experts gathered in Cost European action dedicated to neurology and cardiology-Bioneca, we present the experience acquired by working on two rather different organs: the brain and the heart. When taken into account that diseases of these two organs, mostly ischemic in their nature (stroke and heart infarction), bring by far the largest burden of the medical systems around Europe, it is not surprising that in vitro models of nervous and heart muscle tissue were in the focus of biomedical research in the last decades. In this review we describe and discuss hurdles which still impair further progress of regenerative neurology and cardiology and we detect those ones which are common to both fields and some, which are field-specific. With the goal to elucidate strategies which might be shared between regenerative neurology and cardiology we discuss methodological solutions which can help each of the fields to accelerate their development.

Nitric Oxide and Oxidative Stress-Mediated Cardiovascular Functionality: From Molecular Mechanism to Cardiovascular Disease

The underlying pathology of most cardiovascular diseases (CVDs) such as coronary artery disease, high blood pressure, and stroke involves decreased cardiovascular contractility and anatomic alterations in cardiovascular structures. Nitric oxide (NO) regulates vascular tone and contractile function of myocardium and maintains blood vessel homeostasis. Interestingly, the effect of NO is like a double-edged sword in the body. Insufficient NO causes hypertension and atherosclerosis, while an overproduction of NO may foster inflammation and cause heart infarction and shock. In addition, growing evidences have shown that oxidative stress plays pivotal roles in the initiation and progression of CVDs. This chapter will discuss in detail the roles NO plays in the cardiovascular system under both physiological and pathological conditions. We will focus on: (1) the molecular mechanism of cardiovascular contraction, (2) NO/Ca2+-induced muscle relaxation, (3) NO-related structural change in blood vessels, and (4) redox balance in the cardiovascular system. The relationships between these molecular mechanisms and the characteristics of CVDs will be highlighted.

Reactivation of atrium genes is a primer for heart infarction or regeneration

The inability of the adult heart to repair or regenerate is manifested in prevalent morbidity and mortality related to myocardial infarction and heart failure. However, the cue to the reactivation of cardiomyocyte proliferation in the adult remains largely unknown. In the present study, three independent datasets were explored using bioinformatics analysis methods to solve the problem. Our results revealed that atrium genes were upregulated in response to the injury, which indicates the possible cell type withdraw and reinitiation of proliferation capability. Our findings might provide an alternative viewpoint on the cardiomyocyte regeneration or myocardial infarction.

Prevalence, causes, and complications of acute kidney transplant rejection: survey in a single center

Backgrounds: Kidney transplantation has become a preferred surgical approach for several renal disorders. To acquire required information in basis of acute transplant rejection and its complications, it is important to determine rejection prevalence and its potential causes.Methods: In present retrospective study, during a 37-year survey, 2250 patients received conventional kidney transplantation. The patients who had suffered graft loss, death, and nephrectomy of transplanted kidney during the first month after transplantation enrolled the study and all required data recorded in designed questionnaire. Results: Of 2557 patients underwent kidney transplantation, 86 (3.36%) patients were suffered acute graft loss during the first month after transplantation, that 43 (50%) were males and 43 (50%) were females. Mean age of the patients with acute graft loss was 40.09±14.09. The most common underlying cause for acute graft loss in our study were as follows: acute rejection of transplanted kidney (34.9%), renal vein thrombosis (17.5%), heart infarction (13.9%), idiopathic (6.9%). Of 86 patients, thirty-three patients underwent nephrectomy subsequent to rejection, however, fifty-three patients well responded to medical treatment. In our study the amount of acute nephrectomy during the first month after transplantation was 38.4% (33 patients) which constituted 1.2% of the total graft losses.Conclusion: Renal vein thrombosis is the most common underlying reason for graft loss in kidney transplantation patients, and 1st week of the transplantation is the most probable postoperative time for graft rejection.

Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction

Objectives.Low survival rate of mesenchymal stem cells (MSCs) severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI). Bcl-xL genetic modification might enhance MSC survival after transplantation.Methods.Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs) or empty vector (vector-MSCs). MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISAin vitro.In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery.Results.In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and plate-derived growth factor (PDGF) increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs.In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery.Conclusions.Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

Dental Calculus Is Associated with Death from Heart Infarction

Objectives. We studied whether the amount of dental calculus is associated with death from heart infarction in the dental infection—atherosclerosis paradigm.Materials. Participants were 1676 healthy young Swedes followed up from 1985 to 2011. At the beginning of the study all subjects underwent oral clinical examination including dental calculus registration scored with calculus index (CI). Outcome measure was cause of death classified according to WHO International Classification of Diseases. Unpairedt-test, Chi-square tests, and multiple logistic regressions were used.Results. Of the 1676 participants, 2.8% had died during follow-up. Women died at a mean age of 61.5 years and men at 61.7 years. The difference in the CI index score between the survivors versus deceased patients was significant by the year 2009 (P<0.01). In multiple regression analysis of the relationship between death from heart infarction as a dependent variable and CI as independent variable with controlling for age, gender, dental visits, dental plaque, periodontal pockets, education, income, socioeconomic status, and pack-years of smoking, CI score appeared to be associated with 2.3 times the odds ratio for cardiac death.Conclusions. The results confirmed our study hypothesis by showing that dental calculus indeed associated statistically with cardiac death due to infarction.

Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events), but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and finally an anecdotal muscle-joint pain with self-prescription of non-steroideal anti-inflammatory drugs), represents the key point for a debate around the increasing frequency of “polypharmacy” in the field of HIV infection, even when HIV resistance to antiretroviral is not a concern. The continuing increase of mean age of HIV-infected population, plus the existing, sometimes unmodifiable risk factors for cardiovascular, dysmetabolic, and renal disorders, plus the adjunct of anecdotal illnesses prompting the resort to different drugs and medications, either prescribed for HIV infection itself, or taken for concurrent or subsequent diseases, or self-prescribed occasionally due to an intercurrent, trivial disorders per se, may prompt a complicated scenario culminating with a life-threatening acute renal failure of tubular origin. Our report gives us the opportunity to revise and discuss the expected interactions between antiretroviral therapy and the even growing exposure to multiple different drug and drug classes, which may be responsible for relevant drug interactions and direct or adjunctive end-organ impairment, up to life-threatening conditions, which may be avoided or prevented by considering carefully all comorbidites and co-treatments potentially administered to HIV infected patients, thirty years after the discovery of AIDS.