Harnessing the power of RNA therapeutics in treating ischemic heart failure: the TRAIN-HEART story.

Ischemic heart disease (IHD) is one of the world's foremost killers, accounting for 16% of all deaths worldwide. IHD is the main cause of heart failure (HF), as it leads to pathological changes in the heart, improper pumping function and eventual death. Therapeutic interventions usually follow a systemic general strategy for all heart failure subtypes due to the lack of a deep understanding of the disease mechanisms.

Macrophage-based therapeutic approaches for cardiovascular diseases.

Despite the advances in treatment options, cardiovascular disease (CVDs) remains the leading cause of death over the world. Chronic inflammatory response and irreversible fibrosis are the main underlying pathophysiological causes of progression of CVDs. In recent decades, cardiac macrophages have been recognized as main regulatory players in the development of these complex pathophysiological conditions.

Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model.

Resident cardiac macrophages (rcMACs) are among the most abundant immune cells in the heart. Plasticity and activation are hallmarks of rcMACs in response to changes in the microenvironment, which is essential for in vitro experimentation. The in vivo investigation is confounded by the infiltration of other cells hindering direct studies of rcMACs.

Intercellular transfer of miR-200c-3p impairs the angiogenic capacity of cardiac endothelial cells.

As mediators of intercellular communication, extracellular vesicles containing molecular cargo, such as microRNAs, are secreted by cells and taken up by recipient cells to influence their cellular phenotype and function. Here we report that cardiac stress-induced differential microRNA content, with miR-200c-3p being one of the most enriched, in cardiomyocyte-derived extracellular vesicles mediates functional cross-talk with endothelial cells. Silencing of miR-200c-3p in mice subjected to chronic increased cardiac pressure overload resulted in attenuated hypertrophy, smaller fibrotic areas, higher capillary density, and preserved cardiac ejection fraction.

Non-coding RNAs in cardiac inflammation: key drivers in the pathophysiology of heart failure.

Heart failure is among the most progressive diseases and a leading cause of morbidity. Despite several advances in cardiovascular therapies, pharmacological treatments are limited to relieve symptoms without curing cardiac injury. Multiple observations point to the involvement of immune cells as key drivers in the pathophysiology of heart failure.

Resident cardiac macrophages: crucial modulators of cardiac (patho)physiology.

Resident cardiac macrophages (rcMacs) are integral components of the myocardium where they have key roles for tissue homeostasis and in response to inflammation, tissue injury and remodelling. In this review, we summarize the current knowledge and limitations associated with the rcMacs studies. We describe their specific role and contribution in various processes such as electrical conduction, efferocytosis, inflammation, tissue development, remodelling and regeneration in both the healthy and the disease state.

Non-coding RNAs: update on mechanisms and therapeutic targets from the ESC Working Groups of Myocardial Function and Cellular Biology of the Heart.

Vast parts of mammalian genomes are actively transcribed, predominantly giving rise to non-coding RNA (ncRNA) transcripts including microRNAs, long ncRNAs, and circular RNAs among others. Contrary to previous opinions that most of these RNAs are non-functional molecules, they are now recognized as critical regulators of many physiological and pathological processes including those of the cardiovascular system. The discovery of functional ncRNAs has opened up new research avenues aiming at understanding ncRNA-related disease mechanisms as well as exploiting them as novel therapeutics in cardiovascular therapy.

Therapeutic Delivery of miR-148a Suppresses Ventricular Dilation in Heart Failure.

Heart failure is preceded by ventricular remodeling, changes in left ventricular mass, and myocardial volume after alterations in loading conditions. Concentric hypertrophy arises after pressure overload, involves wall thickening, and forms a substrate for diastolic dysfunction. Eccentric hypertrophy develops in volume overload conditions and leads wall thinning, chamber dilation, and reduced ejection fraction.

Molecular gene profiling of Clostridium botulinum group III and its detection in naturally contaminated samples originating from various European countries.

We report the development of real-time PCR assays for genotyping Clostridium botulinum group III targeting the newly defined C. novyi sensu lato group; the nontoxic nonhemagglutinin (NTNH)-encoding gene ntnh; the botulinum neurotoxin (BoNT)-encoding genes bont/C, bont/C/D, bont/D, and bont/D/C; and the flagellin (fliC) gene. The genetic diversity of fliC among C.

[Symptomatology of tuberculosis].

First described long before the beginning of our era, the clinical presentation of tuberculosis has not really changed much over the course of ages. Although early diagnosis and the introduction of bacteriocidal antibiotics have led to a decline in the most severe forms, at least in developed countries, the general and functional symptomatology, characteristic of chronic tuberculosis, remains unchanged in non-immunodeficient patients. Inversely, in patients with and immunodeficiency syndrome, the distribution and clinical course of the fundamental signs and symptoms have undergone a considerable modification as a result of intercurrent clinical signs of other opportunistic diseases involving both the lung and extrapulmonary organs.

Is intrinsic asthma a hereditary disease?

Although studies of families, inbred populations and twins have established that asthma has a hereditary basis, little evidence has shown that intrinsic asthma has an increased familial occurrence. To document this issue, we compared the prevalence of asthma in families of intrinsic asthmatics, extrinsic asthmatics and non-asthmatics. The intrinsic asthma group included those with negative skin tests to common aero-allergens (n = 117).

[Pleural fibroma: apropos of a case].

The authors report a case of a pleural fibroma occurring in a 72 year old woman. The tumour presented with both an osteoarthropathy and hypoglycaemia. An X-ray revealed an abundant associated pleural effusion.

[Opinions and behavior of asthmatic patients towards treatment using aerosols].

An ever increasing number of drugs prescribed in the treatment of asthma are presented as aerosols, so that patients may be requested to inhale many puffs every day. In this study, the opinion of asthmatic patients was sought and their behaviour towards aerosols during attacks and in long-term treatment was recorded by means of a questionnaire. The answers confirmed that asthmatics liked aerosols and found them usually effective, but 60% of these patients exceeded the stated dose, and if the drug failed to bring the expected relief, 30% waited 24 hours before calling for a doctor.

[Evaluation of the medical costs of asthma in adults during a l-year follow-up in a hospital environment].

The medical cost of asthma is difficult to measure because this syndrome is generally studied in amongst a large group of patients with chronic respiratory disease. The aim of this study was to assess the theoretical cost of the medical treatment of asthma in a group of young adults who are free from any other disease; the study lasted for one year of follow up and the treatment was given in the public hospital service. Four particular situations are identified corresponding to four stages of severity of the disease and each of these stages was given a treatment selected as the usual therapeutic regime given in a respiratory service in a public hospital.

[Aerosol therapy in asthma].

Today there is a general use of aerosols in the treatment of asthma. To understand their importance it is necessary to know the make-up of an aerosol, physical and chemical factors as well as anatomical factors that influence its deposition and clearance in the tracheo-bronchial tree. In the therapy of asthma, small, easy-to-handle and reliable inhalers are prescribed.

[Heredity of asthma].

To compare the heredity of asthma among families of intrinsic, extrinsic and control subjects, we have studied the siblings and offsprings of the 3 groups of subjects (using a standardized questionnaire). The results shown that asthma was genetically transmitted but the clinical manifestations appeared later among the relatives of intrinsic than among the relatives of extrinsic asthmatic patients.

[Diffuse familial interstitial pulmonary fibrosis. Study of a family].

A study of the genealogy of a 53 year old lady (A.M..