Marek Kuch

Sphingolipids in cardiovascular diseases and metabolic disorders

Many investigations suggest the pivotal role of sphingolipids in the pathogenesis of lifestyle diseases such as myocardial infarction, hypertension, stroke, diabetes mellitus type 2 and obesity. Some studies suggest that sphingolipids are important factors in cellular signal transduction. They serve as biologically active components of cell membrane and are involved in many processes such as proliferation, maturation and apoptosis. Recently, ceramide and sphingosine-1-phosphate have become the target of many investigations. Ceramide is generated in three metabolic pathways and many factors induce its production as a cellular stress response. Ceramide has proapoptotic properties and acts as a precursor for many other sphingolipids. Sphingosine-1-phosphate is a ceramide derivative, acting antiapoptotically and mitogenically and it is importantly involved in cardioprotection. Further research on the involvement of sphingolipids in cellular pathophysiology may improve the prevention and therapy of lifestyle diseases.

Cardiovascular magnetic resonance findings in a case of Danon disease

Danon disease is a rare X-linked dominant lysosomal glycogen storage disease that can lead to severe ventricular hypertrophy and heart failure. We report a case of Danon disease with cardiac involvement evaluated with cardiovascular magnetic resonance, including late gadolinium enhancement and perfusion studies.

The Influence of Extreme Mixed Exertion Load on the Right Ventricular Dimensions and Function in Elite Athletes: A Tissue Doppler Study

Aims: The athletes heart is a widely discussed topic regarding the adaptation of the left ventricle (LV) to regular training. The data on the morphology and—even more—the function of the right ventricle (RV) are less well studied. The aim of the study was to assess the influence of prolonged exertion on morphology and function of the RV. Methods and Results: We examined 38 elite athletes, members of the Polish Olympic Team and a control group of 41 age and sex‐matched healthy volunteers. Specifically, we assessed the details of RV size and function including: RV enlargement, transtricuspid systolic gradient, and dilatation of main pulmonary artery (PA) as compared with the values derived from the control group. There was no significant difference in the function of the RV assessed using tissue Doppler echocardiography (TDE) between the athletes and controls (S’: 15.0 cm/sec vs. 14.0 cm/sec; E’: 15.8 cm/sec vs. 15.7 cm/sec; A’: 9.9 cm/sec vs. 10.4 cm/sec), but the athletes had a higher transtricuspid systolic gradient (23.6 mm Hg vs. 19.0 mm Hg, P = 0.004). There were no significant differences in TDE velocities in athletes with dilated RV or PA. However, those with elevated tricuspid regurgitation velocity had lower systolic velocities of the tricuspid annulus then the rest (S’: 12.3 cm/sec vs. 15.5 cm/sec, P = 0.01). Conclusions: RV enlargement in professional athletes is not connected with deterioration of diastolic or systolic RV function. Athletes with elevated pulmonary systolic pressure at rest, however, present with lower longitudinal systolic velocities of RV assessed using TDE. (Echocardiography 2011;28:753‐760)

MicroRNAs: powerful regulators and potential diagnostic tools in cardiovascular disease

1Division of Heart Failure and Cardiac Rehabilitation, Department of Cardiology, Hypertension and Internal Medicine, Second Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland 2Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland 3Genomic Medicine, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland 4Laboratory of Human Cancer Genetics, Centre of New Technologies, CENT, University of Warsaw, Warsaw, Poland

Regulatory mechanisms in arterial hypertension: role of microRNA in pathophysiology and therapy.

Abstract Multiple factors underlie the pathophysiology of hypertension, involving endothelial dysregulation, vascular smooth muscle dysfunction, increased oxidative stress, sympathetic nervous system activation and altered renin -angiotensin -aldosterone regulatory activity. A class of non-coding RNA called microRNA, consisting of 17–25 nucleotides, exert regulatory function over these processes. This paper summarizes the currently available data from preclinical and clinical studies on miRNA in the development of hypertension as well as the impact of anti-hypertensive treatment on their plasma expression. We present microRNAs’ characteristics, their biogenesis and role in the regulation of blood pressure together with their potential diagnostic and therapeutic application in clinical practice.

Effect of different models of cardiac rehabilitation on heart rate recovery

BACKGROUND AND AIM The aim of this study was to assess the effect of different models of the second stage of cardiac rehabilitation on heart rate recovery (HRR). We also evaluated the effect of selected cardiovascular risk factors on HRR. METHODS The study included 103 patients (80 men and 23 women) aged 60.9 ± 10.7 years with a recent acute coronary syndrome undergoing the second stage of a comprehensive cardiac rehabilitation. An exercise test (ExT) was performed before and after rehabilitation. RESULTS HRR improved significantly only in women (26.5 bpm in ExT before rehabilitation vs. 32.8 bpm in ExT after rehabilitation, p < 0.05). The highest HRR was obtained in the subgroup rehabilitated according to the model A, and the lowest in subgroup C (31 vs. 22.1 bpm, p < 0.05). The highest increase in HRR was observed in the most seriously ill patients in subgroup C (18 bpm before rehabilitation vs. 22.1 bpm after rehabilitation). CONCLUSIONS The most significant improvement in HRR was observed in the most seriously ill patients.

Unclassified cardiomyopathy or Lyme carditis? A three year follow-up

Lyme carditis can be a clinical manifestation of the early disseminated stage of Lyme disease caused by the tick-transmitted pathogen Borrelia burgdorferi. We present the case of a 41 year-old Caucasian woman referred to our hospital with symptoms of fatigue, progressive exertional dyspnoea, supraventricular cardiac arrhythmia, and an enlarged heart revealed on chest radiography. Following an untypical result of transthoracic echocardiography, cardiac magnetic resonance was performed. This showed structural cardiac changes and focus of late gadolinium enhancement in the midwall of the apex region. Further diagnostic processes, including endomyocardial biopsy and serology tests, made it possible to diagnose Lyme carditis. Clinical observation was followed-up for three years.

Is atrial fibrillation a risk factor for normal-tension glaucoma?

Abstract Glaucoma (GL) and atrial fibrillation (AF) are diseases of significant social importance. Cardiovascular disorders such as systemic hypertension, hypotension, increased blood viscosity, vasospasm, and diabetes are potential risk factors of GL, especially when intraocular pressure is not elevated. Only a few studies have reported a possible connection between cardiac arrhythmias and GL. The purpose of this study was to evaluate the risk of GL in patients with AF. A total of 117 patients were included in the study, 79 with AF (AF group) and 38 with sinus rhythm (Control group), matched for age and sex. The mean ± standard deviation age was 73.6 ± 7.2 and 71.6 ± 4.7 years for the AF and control groups, respectively. There were no statistically significant differences in the percentage of systemic hypertension, congestive heart failure, diabetes mellitus type 2, or vascular disease between the groups. Patients were examined for the presence of normal-tension glaucoma (NTG) by an ophthalmologist. NTG was confirmed in 40 patients (34.2%) in the entire group, with 35 (44.3%) in the AF group and 5 (13.15%) in the Control group. The incidence of NTG was significantly higher in the AF group (P = .0221). Women represented 60% of GL patients in the AF group and 80% in the control group. There were no significant differences in intraocular pressure between the groups (mean ± standard deviation, 14.3 ± 2.3 vs. 14.2 ± 2.8 mmHg, P = .4202). Approximately three-fourths of patients with AF and NTG had early visual field damage based on the Hodapp classification. AF, independent of other known cardiovascular risk factors, increases the risk of developing NTG. Many AF patients do not have conspicuous symptoms of GL, so understanding the possible risk of its development is critical because early detection might help to prevent later visual impairment and even irreversible blindness.

The role of apelin in central cardiovascular regulation in rats with post-infarct heart failure maintained on a normal fat or high fat diet.

Based on the available literature, it can be assumed that in cases of post‐infarct heart failure (HF) and obesity, a significant change in the central regulation of the cardiovascular system takes place with, among others, the involvement of the apelinergic system. The main objective of the present study was to clarify the role of apelin‐13 in the central regulation of the cardiovascular system in Sprague Dawley rats with HF or sham operated (SO) and fed on a normal fat (NFD) or a high fat diet (HFD). The study was divided into two parts: Part I, hemodynamic studies; and Part II, biochemical and molecular studies. The animals were subjected to the following research procedures. Part I and II: feeding NFD or HFD; experimental induction of HF or SO; Part I: intracerebroventricular (ICV) infusion of the examined substances, monitoring of mean arterial blood pressure (MABP) and heart rate (HR); Part II: venous blood and tissue samples collected. ICV infusion of apelin‐13 caused significantly higher changes in ΔMABP in the SO NFD group. No changes were noted in ΔHR in any of the studied groups. Apelin and apelin receptor (APJ) mRNA expression in the brain and adipose tissues was higher in the HF rats. HFD causes significant increase in expression of apelin and APJ mRNA in the left ventricle. In conclusion, HF and HFD appear to play an important role in modifying the activity of the central apelinergic system and significant changes in mRNA expression of apelin and APJ receptor.

Increased Activity of the Intracardiac Oxytocinergic System in the Development of Postinfarction Heart Failure

Aim. The present study was designed to test the hypothesis that the development of postinfarction heart failure is associated with a change of activity of the intracardiac oxytocinergic system. Methods. Experiments were performed on male Sprague-Dawley rats subjected to myocardial infarction or sham surgery. Four weeks after the surgery, blood samples were collected and the samples of the left ventricle (LV) and right ventricle (RV) were harvested for evaluation of the mRNA expression (RT-PCR) of oxytocin (OT), oxytocin receptor (OTR), natriuretic peptides, and the level of OT and OTR protein (ELISA). The concentration of N-terminal B-type natriuretic peptide was measured to determine the presence of heart failure. Results. Plasma NT-proBNP concentration was higher in the infarcted rats. In the infarcted rats, the expression of OT mRNA and the OT protein level were higher in the RV. There were no significant differences between infarcted and noninfarcted rats in the expression of OT mRNA and in the OT protein level in the fragments of the LV. In both the left and the right ventricles, OTR mRNA expression was lower but the level of OTR protein was higher in the infarcted rats. Conclusions. In the present study, we indicate that postinfarction heart failure is associated with an increased activity of the intracardiac oxytocinergic system.