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István Kovanecz

István Kovanecz
The Lundquist Institute · Surgery

PhD

About

79
Publications
8,871
Reads
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1,662
Citations
Introduction
I am currently working on defining biomarkers for the stem cell damage caused by a noxious systemic environment (hyperglycemia, hyperlipidemia, etc.). Predicting the impairment of the stem cells' repair capacity and finding a possible in vitro correction before the implantation would improve the efficacy of autologous stem cell therapies.
Additional affiliations
January 2020 - present
California State University, Dominguez Hills
Position
  • Lecturer
September 2019 - present
The Lundquist Institute for Biomedical Innovations at Harbor-UCLA Medical Center
Position
  • Investigator
Description
  • Preclinical animal studies for sexual dysfunction, skeletal and cardiovascular muscle regeneration, and diabetes-related complications.
May 2013 - June 2013
FDA National Center for Toxicological Research (NCTR)
Position
  • Visiting Research Scientist
Description
  • Participated in a multicenter animal study.
Education
August 1991 - January 1994
József Attila University of Arts and Sciences(JATE), Szeged, Hungary
Field of study
  • Comparative Physiology
September 1979 - June 1985
József Attila University of Arts and Sciences(JATE), Szeged, Hungary
Field of study
  • Biology

Publications

Publications (79)
Article
To determine, in the obese Zucker fa/fa rat (OZR), whether the loss in smooth muscle cells (SMCs) as well as the increase in fibrosis that occurs within the corpora cavernosa accompanying corporal veno-occlusive dysfunction (CVOD), also occurs within the media of the arterial tree. The penis and aorta from both 7-month-old male diabetic OZR (5 mont...
Article
INTRODUCTION AND OBJECTIVE: Arteriosclerosis or fibrosis of the arterial media is a common complication of type 2 diabetes mellitus, as is erectile dysfunction. Utilizing the Zucker fa/fa rat as a model for type 2 diabetes, which has previously been shown to develop erectile dysfunction 5 months after the onset of diabetes, we investigated whether:...
Article
INTRODUCTION AND OBJECTIVE: We have shown that CVOD and moderate corporal fibrosis occur in the obese Zucker fa/fa rat (OZR), an animal model of morbid obesity, and type 2 diabetes with mild hyperglycemia. We also reported that both the OZR and the Zucker diabetic fa/fa rat (ZDFR), a related strain with severe hyperglycemia, low serum testosterone...
Article
To determine whether corporal veno-occlusive dysfunction (CVOD), corporal smooth muscle (SM) loss, fibrosis and oxidative stress occur in a rat model of type 2 diabetes, and whether these are counteracted by pioglitazone, as pioglitazone is vasculoprotective, and corporal SM is an extension of arterial SM. Male obese Zucker fa/fa rats were fed chow...
Article
Bisphenol A (BPA), a suspected reproductive biohazard and endocrine disruptor, released from plastics is associated with ED in occupationally exposed workers. However, in rats, despite the induction of hypogonadism, apoptosis of the penile corporal smooth muscle (SM), fat infiltration into the cavernosal tissue and changes in global gene expression...
Article
Full-text available
Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performed with stem cell autografts, exposed to the noxious T2D/O milieu, often with suboptimal results. We showed in the Obese Zucker (OZ) rat model of T2D/O that when their muscle-derived stem cells (MDSC) were from long-term T2D/O male rats, their repair efficacy for er...
Article
Full-text available
Female stress urinary incontinence (FSUI) is prevalent in women with type 2 diabetes/obesity (T2D/O), and treatment is not optimal. Autograph stem cell therapy surprisingly has poor efficacy. In the male rat model of T2D/O, it was demonstrated that epigenetic changes, triggered by long-term exposure to the dyslipidemic milieu, led to abnormal globa...
Conference Paper
Full-text available
Introduction: Female stress urinary incontinence (FSUI) is prevalent in women with type 2 diabetes/obesity (T2D/O), and treatment is not optimal. Stem cells (SC) may repair endogenously the damaged bladder urethral myosphincter (BUM), but have poor efficacy in SC therapy, usually as autografts. In the male Zucker fatty (ZF) rat model of T2D/O with...
Article
Full-text available
Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the field but many hurdles still remain, which may require new ideas and collaborations. In 2012 a web-based effort cal...
Article
Full-text available
Background: Previous work showed that muscle-derived stem cells (MDSCs) exposed long-term to the milieu of uncontrolled type 2 diabetes (UC-T2D) in male obese Zucker (OZ) rats, were unable to correct the associated erectile dysfunction and the underlying histopathology when implanted into the corpora cavernosa, and were also imprinted with a noxiou...
Conference Paper
Introduction. Potential stem cell damage by a disease-induced milieu, and its risks of impaired stem cell therapy, have not virtually been explored so far in either research or therapy. However, it was recently reported that muscle derived stem cells (MDSC) isolated at a late stage diabetes (LD-MDSC) from aged Zucker obese (ZO) rats after their end...
Article
Myostatin is present in striated myofibers but, except for myometrial cells, has not been reported within smooth muscle cells (SMC). We investigated in the rat whether myostatin is present in SMC within the penis and the vascular wall and, if so, whether it is transcriptionally expressed and associated with the loss of corporal SMC occurring in cer...
Conference Paper
Objectives: Clinical trials demonstrate that clostridium histolyticum collagenase (CHC) intraplaque injection (Xiaflex) is an effective therapy for correcting the curvature associated with Peyronie’s disease (PD). Since the myofibroblast is the cell within the plaque that is responsible for plaque formation, and its persistence may lead to recurren...
Article
Full-text available
Background Critical Limb Ischemia (CLI) affects patients with Type 2 Diabetes (T2D) and obesity, with high risk of amputation and post-surgical mortality, and no effective medical treatment. Stem cell therapy, mainly with bone marrow mesenchymal, adipose derived, endothelial, hematopoietic, and umbilical cord stem cells, is promising in CLI mouse a...
Article
Full-text available
Nature Communications 7: Article number:1254910.1038/ncomms12549 (2016); Published September 16 2016; Updated October 25 2016 The original version of this Article contained an error in the spelling of a member of the University of Michigan students Consortium, Sam Lee, which was incorrectly given as Sam Lewe. This has now been corrected in both th...
Article
Introduction: Muscle-derived stem cells (MDSCs) and other SCs implanted into the penile corpora cavernosa ameliorate erectile dysfunction in type 1 diabetic rat models by replenishing lost corporal smooth muscle cells (SMCs) and decreasing fibrosis. However, there are no conclusive data from models of type 2 diabetes (T2D) and obesity. Aim: To d...
Article
IntroductionThe success of medical therapies for Peyronie's disease (PD) has not been optimal, possibly because many of them went directly to clinical application without sufficient preclinical scientific research. Previous studies revealed cellular and molecular pathways involved in the formation of the PD plaque and in particular the role of the...
Article
Full-text available
Erectile dysfunction is a common complication for patients undergoing surgeries for prostate, bladder, and colorectal cancers, due to damage of the nerves associated with the major pelvic ganglia (MPG). Functional re-innervation of target organs depends on the capacity of the neurons to survive and switch towards a regenerative phenotype. PDE5 inhi...
Article
Abstract Bisphenol A is an environmental toxin released from plastics and has been shown to directly affect the coronary arteries and smooth muscle resulting in cardiac dysfunction leading to an increase in arrhythmias and coronary artery disease. Positive correlations between chemical dose exposure and increases in blood pressure have also been o...
Article
Myostatin is present in striated myofibers but, except for myometrial cells, has not been reported within smooth muscle cells (SMC). We investigated in the rat whether myostatin is present in SMC within the penis and the vascular wall and, if so, whether it is transcriptionally expressed and associated with the loss of corporal SMC occurring in cer...
Article
Bisphenol A (BPA), released from plastics and dental sealants, is a suspected endocrine disruptor and reproductive toxicant. In occupationally exposed workers, BPA has been associated with erectile dysfunction (ED). To determine whether long-term exposure to high doses of BPA in the rat affects serum levels of testosterone (T) and estradiol (E2), a...
Article
Full-text available
INTRODUCTION AND OBJECTIVES Bisphenol A (BPA), a suspected reproductive biohazard/endocrine disruptor released from plastics and dental sealants, has been associated with erectile dysfunction (ED) in exposed workers. However, in male rats, daily intraperitoneal administration of BPA for 3 months induced hypogonadism, mild cavernosal lipo-fibrosis a...
Article
Full-text available
Introduction Stimulating the commitment of implanted dystrophin+ muscle-derived stem cells (MDSCs) into myogenic, as opposed to lipofibrogenic lineages, is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD). Methods To examine whether counteracting myostatin, a negative regulator of muscle mass and a pro-lipofibrotic factor, wo...
Article
Introduction: Long-term daily administration of phosphodiesterase type 5 (PDE5) inhibitors in the rat prevents or reverses corporal veno-occlusive dysfunction (CVOD) and smooth muscle cell (CSMC) loss and fibrosis, in both aging and bilateral cavernosal nerve resection (BCNR) models for erectile dysfunction. In the aging rat model, corporal implan...
Article
Full-text available
Previous studies have shown that long-term oral daily PDE 5 inhibitors (PDE5i) counteract fibrosis, cell loss, and the resulting dysfunction in tissues of various rat organs and that implantation of skeletal muscle-derived stem cells (MDSC) exerts some of these effects. PDE5i and stem cells in combination were found to be more effective in non-MI c...
Article
Objective: To determine the gene expression profile of pelvic ganglia neurones after bilateral cavernosal nerve resection (BCNR) and subsequent treatment with sildenafil in relation to neurotrophic-related pathways. Materials and methods: Fisher rats aged 5 months were subjected to BCNR or sham operation and treated with or without sildenafil (2...
Article
Introduction. It has been shown that phosphodiesterase type 5 (PDE5) inhibitors preserve smooth muscle (SM) content and ameliorate the fibrotic degeneration normally seen in the corpora cavernosa after bilateral cavernosal nerve resection (BCNR). However, the downstream mechanisms by which these drugs protect the corpora cavernosa remain poorly und...
Article
INTRODUCTION AND OBJECTIVES: Long-term daily administration of any of the PDE5 inhibitors (PDE5i) in the rat prevents or reverses corporal smooth muscle cell (SMC) apoptosis, fibrosis and CVOD in both aging and cavernosal nerve resection (BCNR) models for erectile dysfunction (ED). In the aging rat model, corporal implantation of MDSC reverses CVOD...
Article
INTRODUCTION AND OBJECTIVES: Cavernosal Veno-occlusive dysfunction (CVOD) which normally occurs when there is both a loss of smooth muscle cells together with an increase in fibrosis within the corpora cavernosa, can be experimentally induced by an injury to the cavernosal nerves. We examined the use of telemetric monitoring of the intracavernosal...
Article
INTRODUCTION AND OBJECTIVES: Erectile dysfunction is one of the complications associated with radical prostatectomy (RP) due to damage of the cavernosal nerves. The treatment with phosphodiesterase 5 (PDE5) inhibitors such as sildenafil preserves penile corporal smooth muscle and ameliorates fibrotic degeneration normally seen after bilateral caver...
Article
INTRODUCTION AND OBJECTIVES: We have previously demonstrated that long term treatment with PDE 5 inhibitors preserves corporal smooth muscle and ameliorates fibrotic degeneration normally seen after bilateral cavernosal nerve resection (BCNR) in rats. However, the mechanism by which these drugs promote corporal protection remains poorly understood....
Article
Goal: to investigate the role of myostatin (Mst) in adult skeletal muscle structure, function and physical performance. We generated the conditional Mst overexpressing transgenic (CMOT) mice in which Mst expression can be switched ON or OFF. Methods: We used mechanical overloading (MO) (bilateral synergist ablation of plantaris muscle) to determine...
Article
Grafts are used for vaginal repair after prolapse, but their use to carry stem cells to regenerate vaginal tissue has not been reported. In this study, we investigated whether 1) muscle-derived stem cells (MDSC) grown on small intestinal submucosa (SIS) generate smooth-muscle cells (SMC) in vitro and upon implantation in a rat model of vaginal defe...
Article
INTRODUCTION AND OBJECTIVE: Very small embryonic-like (VSEL) stem cells expressing embryonic markers, specifically Oct 4, have recently been found in many adult organs. We have previously isolated endogenous multipotent cells from the human penile tunica albuginea, and detected cells in the rat tunica albuginea and corpora cavernosa that express st...
Article
Corporal veno-occlusive dysfunction (CVOD), which usually is associated with a loss of smooth muscle cells (SMC) and an increase in fibrosis within the corpora cavernosa, can be induced by an injury to the cavernosal nerves. The corporal tissue expresses inducible nitric oxide synthase (iNOS), presumably as an antifibrotic and SMC-protective respon...
Article
To determine whether skeletal muscle-derived stem cells (MDSCs) convert into smooth muscle cells (SMCs) both in vitro and in vivo, and in so doing ameliorate the erectile dysfunction (ED) of aged rats, and whether endogenous stem cells are present in the rat corpora cavernosa. MDSCs were obtained from mouse muscle, and shown by immunocytochemistry...
Article
INTRODUCTION AND OBJECTIVE: The repair of vaginal tissue after vaginal vault prolapse or for correcting genital abnormalities is based on surgical techniques with graft materials that are under constant development. However, in contrast to other approaches in female pelvic reconstruction, stem cells have not yet been tested for this purpose in the...
Article
It was recently reported in the rat that vardenafil given in a continuous long-term manner was successful in preventing smooth muscle fibrosis in the penile corpora cavernosa and corporal veno-occlusive dysfunction (CVOD) that occur following bilateral cavernosal nerve resection (BCNR), a model for human erectile dysfunction after radical prostatec...
Article
To determine whether a long-term single daily oral dose of a longer half-life phosphodiesterase-5 (PDE5) inhibitor, tadalafil, has a similar effect to that of the shorter half-life PDE5 inhibitors sildenafil and vardenafil, and can prevent the fibrosis and resultant corporal veno-occlusive dysfunction (CVOD) occurring after cavernosal nerve (CN) in...
Article
Erectile dysfunction (ED) is a common complication after radical prostatectomy and results from trauma sustained by the cavernosal nerves. This is a major concern for patients and often affects treatment decisions. The likely mechanism for post-prostatectomy ED is through corporal veno-occlusive dysfunction. There is an increasing amount of evidenc...
Article
To determine whether ageing-related changes in the penile corpora cavernosa, namely corporal veno-occlusive dysfunction (CVOD), loss of smooth muscle cells (SMCs), and excessive collagen deposition, can be ameliorated by the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist pioglitazone, in a rat model of ageing as we have shown...
Article
Aging-related erectile dysfunction is characterized by a loss of smooth muscle cells (SMCs) and fibrosis in the corpora cavernosa, and functionally by corporal veno-occlusive dysfunction (CVOD). Phosphodiesterase 5 (PDE5A) inhibitors, in part via upregulating inducible nitric oxide synthase (NOS2A), have antifibrotic properties in penile tissues. W...
Article
Over-expression of penile neuronal nitric oxide synthase (PnNOS) from a plasmid ameliorates aging-related erectile dysfunction (ED), whereas over-expression of the protein inhibitor of NOS (PIN), that binds to nNOS, increases ED. To improve this form of gene therapy for ED by comparing the electrical field response of short hairpin RNA (shRNA) for...
Article
Impotence, specifically corporal veno-occlusive dysfunction (CVOD), occurs after radical prostatectomy. It results from the effects of cavernosal nerve damage, which causes smooth muscle (SM) loss and an increase in collagen within the corpora. Recent reports have suggested that long-term treatment with phosphodiesterase-5 inhibitors after radical...
Article
To determine whether the phosphodiesterase-5 (PDE5) inhibitor, vardenafil, given orally and in different regimens, has a similar effect to that of the PDE5 inhibitor sildenafil, which prevented the development of a Peyronie's disease (PD)-like plaque formation induced by injecting transforming growth factor beta1 (TGF-beta1) into the tunica albugin...
Article
The acute and chronic effects of pranidipine, a long-acting calcium channel blocker, were examined in three models of cardiac ischemia. In anesthetized dogs, an intracoronary endothelin-1 (ET-1) decreased coronary blood flow (CBF) and maximal first derivative of left ventricular pressure (LVdP/dt max), increased left ventricular end-diastolic press...
Article
The antiischemic effect of drugs can be detected at a lower dose range if the cardiac workload is increased. A brief period of frequency-loading (ventricular overpacing = VOP) results in well-defined, reproducible changes in cardiac parameters in the conscious, chronically instrumented rabbit; however, rapid pacing frequently evoked ventricular tac...
Article
In the present study we tested the preconditioning effect of repeated beta adrenergic stress induced by Isoproterenol in chronically instrumented, conscious rabbits. We have found that at least 5 intravenous administrations of Isoproterenol, repeated at 10 min intervals, were necessary to induce a long-term cardiac adaptation manifested by a signif...
Conference Paper
It was shown by us earlier that a single dose of ILOPROST afforded a dose- and time-dependent protection against the consequences of global myocardial ischaemia induced by intravenous injection of ISOPROTERENOL, a beta-adrenergic agonist. In the present study we tested PHENYLEPHRINE, an alpha-adrenergic agonist, in a dose of 16 µg/kg under the same...
Article
We studied the level of the cytotoxic anti-HLA antibodies (CTA) in 90 hemodialyzed chronic uraemic patients who were on waiting list of transplantation. An association between alleles of HLA A1, B8, DR3 haplotype and the level of CTA was studied. The ratio of the reduced CTA producing subjects was significantly higher in the HLA B8 and DR3 carriers...
Article
The pattern electroretinogram (PERG) has been previously shown to be sensitive to dopaminergic manipulations in the monkey's retina. In order to study the role of retinal D2 receptors we recorded the PERG before and during the acute administration of l-sulpiride, a selective D2 blocker, in three monkeys. The stimuli were sinusoidal vertical grating...
Article
We studied the acute effect of cholinergic agents, scopolamine alone and scopolamine pretreatment and acetyl-L-carnitine (ALC) on visual event-related potentials (ERPs) in a monkey performing in a go/no-go visual oddball discrimination task. The same monkey was studied repeatedly for a period extending over 1.5 years. Scopolamine is known to cause...
Article
We studied in-vitro steroid sensitivity using the test of ADCC in 207 haemodialysed chronic uremic patients, 85 renal transplant patients, and 75 healthy blood donors as normal controls. The association of HLA phenotypes with the in-vitro steroid sensitivity was assessed. The proportion of steroid-sensitive subjects was significantly higher in the...