A5072358528- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Cardiac Fibrosis and Remodeling
- Mitochondrial Function and Pathology
- Regulation of Appetite and Obesity
- Connective Tissue Growth Factor Research
- Cardiac Ischemia and Reperfusion
- Pulmonary Hypertension Research and Treatments
- Apelin-related biomedical research
- Connective tissue disorders research
- Cardiovascular Function and Risk Factors
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- High Altitude and Hypoxia
- Congenital heart defects research
- Cardiac electrophysiology and arrhythmias
- Biochemical Analysis and Sensing Techniques
- Adipokines, Inflammation, and Metabolic Diseases
- Tissue Engineering and Regenerative Medicine
- Adipose Tissue and Metabolism
- Cancer, Lipids, and Metabolism
- Cardiac Arrhythmias and Treatments
- Angiogenesis and VEGF in Cancer
- melanin and skin pigmentation
- Molecular Biology Techniques and Applications
University of Oulu
2015-2025
Oulu University Hospital
2014-2021
Bay Zoltán Foundation for Applied Research
2019
Gottsegen National Cardiovascular Center
2011-2016
FibroGen (United States)
2014
University of Helsinki
2014
University of Pecs
2006
Rutgers, The State University of New Jersey
1999
Johnson University
1999
Semmelweis University
1982
Connective tissue growth factor (CTGF) is involved in the pathogenesis of various fibrotic disorders. However, its role heart not clear. To investigate CTGF regulating development cardiac fibrosis and failure, we subjected mice to thoracic aortic constriction (TAC) or angiotensin II infusion, antagonized function with monoclonal antibody (mAb). After 8 weeks TAC, treated mAb had significantly better preserved left ventricular (LV) systolic reduced LV dilatation compared control...
Myocardial infarction (MI)-induced cardiac fibrosis attenuates contractile function, and predisposes to arrhythmias sudden death. Expression of connective tissue growth factor (CTGF) is elevated in affected organs virtually every fibrotic disorder the diseased human myocardium. Mice were subjected treatment with a CTGF monoclonal antibody (mAb) during infarct repair, post-MI left ventricular (LV) remodeling, or acute ischemia-reperfusion injury. mAb therapy repair improved survival reduced...
Abstract The members of lethal‐7 (Let‐7) micro RNA (mi ) family are involved in regulation cell differentiation and reprogramming somatic cells into induced pluripotent stem cells. However, their function the heart is not known. In this study, we examined effect inhibiting Let‐7c mi on progression postinfarction left ventricular (LV) remodeling mice. Myocardial infarction was with permanent ligation anterior descending coronary artery a 4‐week follow‐up period. inhibited specific antagomir...
Small-molecule inhibition of hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) is being explored for the treatment anemia. Previous studies have suggested that HIF-P4H-2 may also protect heart from an ischemic insult. Hif-p4h-2(gt/gt) mice, which 76 to 93% knockdown Hif-p4h-2 mRNA in endothelial cells, fibroblasts, and cardiomyocytes normoxic stabilization Hif-α, were subjected ligation left anterior descending coronary artery (LAD). deficiency resulted increased survival,...
Transcription factors are fundamental regulators of gene transcription, and many diseases, such as heart associated with deregulation transcriptional networks. In the adult heart, zinc-finger transcription factor GATA4 is a critical regulator cardiac repair remodelling. Previous studies also suggest that NKX2-5 plays function role cofactor GATA4. We have recently reported identification small molecules either inhibit or enhance GATA4-NKX2-5 synergy. Here, we examined actions potent inhibitor...
Apelin levels decline with age. This study demonstrates that in trained mice, apelin deficiency results a switch from fast type II myofibers to slow oxidative I myofibers. is associated concomitant change gene expression profile toward fatty acid utilization, indicating an aged-muscle phenotype exercised apelin-deficient mice. These data are of importance the design exercise programs for aging individuals and could offer therapeutic target maintain muscle mass.
Background The melanocortin 1 receptor (MC1R) is abundantly expressed in the skin and leukocytes, where it regulates pigmentation inflammatory responses. Recently, MC1R was also found heart, but its functional role has remained unknown. We aimed to investigate whether involved regulation of pathological or physiological cardiac remodeling. Methods Results Recessive yellow mice, as a model global deficiency, cardiomyocyte‐specific knockout mice were subjected transverse aortic constriction...
Background Activation of the renin-angiotensin-system (RAS) plays a key pathophysiological role in heart failure patients with hypertension and myocardial infarction. However, function (pro)renin receptor ((P)RR) is not yet solved. We determined here direct functional structural effects (P)RR heart. Methodology/Principal Findings was overexpressed by using adenovirus-mediated gene delivery normal adult rat hearts up to 2 weeks. into anterior wall left ventricle decreased ejection fraction...
Activin A and myostatin, members of the transforming growth factor (TGF)-β superfamily secreted factors, are potent negative regulators muscle growth, but their contribution to myocardial ischemia-reperfusion (IR) injury is not known. The aim this study was investigate if activin 2B (ACVR2B) receptor ligands contribute IR injury. Mice were treated with soluble ACVR2B decoy (ACVR2B-Fc) subjected ischemia followed by reperfusion for 6 or 24 h. Systemic blockade ACVR2B-Fc protective against...
Abstract Hypoxia plays an important regulatory role in the vasculature to adjust blood flow meet metabolic requirements. At level of gene transcription, responses are mediated by hypoxia-inducible factor (HIF) stability which is controlled HIF prolyl 4-hydroxylase-2 (PHD2). In lungs hypoxia results vasoconstriction, however, pathophysiological relevance PHD2 major arterial cell types; endothelial cells (ECs) and smooth muscle (aSMCs) adult incompletely characterized. Here, we investigated...
Doxorubicin is a widely used anticancer drug that causes dose-related cardiotoxicity. The exact mechanisms of doxorubicin toxicity are still unclear, partly because most in vitro studies have evaluated the effects short-term high-dose treatments. Here, we developed an model long-term low-dose administration utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Moreover, given current strategies for prevention and management doxorubicin-induced cardiotoxicity fail...
Recent studies suggest that the ubiquitin-specific protease USP28 plays an important role in cellular repair and tissue remodeling, which implies it has a direct carcinogenesis. The carcinogenic potential of was investigated comprehensive manner using patients, animal models, cell culture. findings demonstrate overexpression correlates with better survival patients invasive ductal breast carcinoma. Mouse xenograft experiments USP28-deficient cancer cells also support this view. Furthermore,...
Sprouty1 (Spry1) is a negative modulator of receptor tyrosine kinase signaling, but its role in cardiomyocyte survival has not been elucidated. The aim this study was to investigate the potential Spry1 cardiac ischemia-reperfusion (I/R) injury. Infarct areas mouse hearts showed an increase protein expression, which localized cardiomyocytes. To if regulates I/R injury, 8-week-old inducible knockout (Spry1 cKO) mice and control were subjected cKO reduction release troponin I reduced infarct...
Cardiac fibrosis stiffens the ventricular wall, predisposes to cardiac arrhythmias and contributes development of heart failure. In present study, our aim was identify novel miRNAs that regulate could serve as potential therapeutic targets for myocardial fibrosis.Analysis samples from sudden death victims with extensive primary cause identified dysregulation miR-185-5p. Analysis resident cells mice subjected experimental model showed induction miR-185-5p expression specifically in...
The phosphatase and actin regulator 1 (PHACTR1) locus is a very commonly identified hit in genome-wide association studies investigating coronary artery disease myocardial infarction (MI). However, the function of PHACTR1 heart still unknown. We characterized mechanisms regulating Phactr1 expression heart, used adenoviral gene delivery to investigate effects on cardiac function, analyzed relationship between MI associated allele human subjects. mRNA protein levels were markedly reduced (60%,...
Blockade of activin 2 receptor (ACVR2) signaling has been shown to improve insulin sensitivity and aid in weight loss. Inhibition ACVR2 restores cardiac function multiple heart failure models. However, its potential the treatment obesity-related cardiometabolic disease remains unknown. Here, we investigated targeting manifested with metabolic dysfunction-associated steatotic liver (MASLD).
Abstract In this study, we investigated whether local intramyocardial GATA4 overexpression affects the left ventricular (LV) remodelling process and importance of phosphorylation at serine 105 (S105) for actions in an angiotensin II (AngII)‐induced hypertension rat model. Adenoviral constructs overexpressing wild‐type or mutated S105 were delivered into anterior LV free wall. AngII (33.3 µg/kg/h) was administered via subcutaneously implanted minipumps. Cardiac function structure examined by...
The elasticity of tissues subjected to repeated deformation is provided by the presence elastic fibers in extracellular matrix (ECM). most abundant component elastin, whose soluble precursor tropoelastin. To establish role elastin plays bladder, this study describes biosynthetic, histologic, and physiologic consequences expression an isoform rat tropoelastin transgenic mouse bladder. polymerase chain reaction (PCR) was used determine a minigene mice. Histochemical methods were demonstrate...
Abstract Mcl-1 is highly expressed in a variety of human cancers (including those hematopoietic and lymphoid origin) exploited by cancer cells to evade cell death develop resistance diverse chemotherapeutic agents. We disclose, for the first time, structure S64315 (also named MIK665) potent selective inhibitor with improved potency over its predecessor S63845 (Kotschy et al, Nature, 2016). S64315/MIK665 currently phase 1 AML (Acute Myeloid Leukemia) MDS (Myelodysplastic Syndrome) (EudraCT...
Abstract α-Melanocyte-stimulating hormone (α-MSH) regulates diverse physiological functions by activating melanocortin receptors (MC-R). However, the role of α-MSH and its possible target in heart remain completely unknown. Here we investigate whether could be involved pathological cardiac remodeling. We found that was highly expressed mouse with reduced ventricular levels after transverse aortic constriction (TAC). Administration a stable analog protected mice against TAC-induced...