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Book: HYPERTENSIVE EFFECT OF AUTOIMMUNE NEPHRITIS IN DOCA-NACL-TREATED AND IN SPONTANEOUSLY HYPERTENSIVE RATS

Tikkanen, Ilkka

1981

Size	36 S.
Document type	Book
Note	HELSINKI, UNIV., DISS., 1981
HBZ-ID	HT002716794
ISBN	951-99301-5-9 ; 978-951-99301-5-2
Database	Catalogue ZB MED Medicine, Health

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Article: Minkä valitsen ensimmäiseksi verenpainelääkkeeksi?

Tikkanen, Ilkka

Duodecim; laaketieteellinen aikakauskirja

2010 Volume 126, Issue 8, Page(s) 891–896

Abstract: All pivotal groups of antihypertensive drugs improve the prognosis of hypertensive patients. The status of renin-angiotensin system inhibitors as the first-line drug has become established in high-risk patients. Antihypertensive efficacy of various drugs ...

Title translation	Which one to choose for the first antihypertensive drug?.
Abstract	All pivotal groups of antihypertensive drugs improve the prognosis of hypertensive patients. The status of renin-angiotensin system inhibitors as the first-line drug has become established in high-risk patients. Antihypertensive efficacy of various drugs varies individually due to the diversity of the background of hypertension and the heterogeneous nature of essential hypertension, whereby choice of the first-line drug is made on an individual basis. The selection involves consideration of predictive evidence of possible target organ alterations and associated diseases with various drug classes on one hand and factors affecting the patient's individual blood pressure response on the other hand.
MeSH term(s)	Antihypertensive Agents/therapeutic use ; Decision Making ; Humans ; Hypertension/drug therapy ; Renin-Angiotensin System/drug effects
Chemical Substances	Antihypertensive Agents
Language	Finnish
Publishing date	2010
Publishing country	Finland
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	127604-9
ISSN	0012-7183
ISSN	0012-7183
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Article ; Online: Deficiency of heme oxygenase 1a causes detrimental effects on cardiac function.

Wang, Hong / Siren, Juuso / Perttunen, Sanni / Immonen, Katariina / Chen, Yu-Chia / Narumanchi, Suneeta / Kosonen, Riikka / Paavola, Jere / Laine, Mika / Tikkanen, Ilkka / Lakkisto, Päivi

Journal of cellular and molecular medicine

2024 Volume 28, Issue 7, Page(s) e18243

Abstract: Humans lacking heme oxygenase 1 (HMOX1) display growth retardation, haemolytic anaemia, and vulnerability to stress; however, cardiac function remains unclear. We aimed to explore the cardiac function of zebrafish lacking hmox1a at baseline and in ... ...

Abstract	Humans lacking heme oxygenase 1 (HMOX1) display growth retardation, haemolytic anaemia, and vulnerability to stress; however, cardiac function remains unclear. We aimed to explore the cardiac function of zebrafish lacking hmox1a at baseline and in response to stress. We generated zebrafish hmox1a mutants using CRISPR/Cas9 genome editing technology. Deletion of hmox1a increases cardiac output and further induces hypertrophy in adults. Adults lacking hmox1a develop myocardial interstitial fibrosis, restrain cardiomyocyte proliferation and downregulate renal haemoglobin and cardiac antioxidative genes. Larvae lacking hmox1a fail to respond to hypoxia, whereas adults are insensitive to isoproterenol stimulation in the heart, suggesting that hmox1a is necessary for cardiac response to stress. Haplodeficiency of hmox1a stimulates non-mitochondrial respiration and cardiac cell proliferation, increases cardiac output in larvae in response to hypoxia, and deteriorates cardiac function and structure in adults upon isoproterenol treatment. Intriguingly, haplodeficiency of hmox1a upregulates cardiac hmox1a and hmox1b in response to isoproterenol. Collectively, deletion of hmox1a results in cardiac remodelling and abrogates cardiac response to hypoxia and isoproterenol. Haplodeficiency of hmox1a aggravates cardiac response to the stress, which could be associated with the upregulation of hmox1a and hmox1b. Our data suggests that HMOX1 homeostasis is essential for maintaining cardiac function and promoting cardioprotective effects.
MeSH term(s)	Animals ; Humans ; Heme Oxygenase (Decyclizing) ; Zebrafish/genetics ; Isoproterenol/pharmacology ; Heme Oxygenase-1/genetics ; Myocardium ; Cardiomyopathies ; Hypoxia ; Myocytes, Cardiac
Chemical Substances	Heme Oxygenase (Decyclizing) (EC 1.14.14.18) ; Isoproterenol (L628TT009W) ; Heme Oxygenase-1 (EC 1.14.14.18)
Language	English
Publishing date	2024-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.18243
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Article: Zebrafish Heart Failure Models.

Narumanchi, Suneeta / Wang, Hong / Perttunen, Sanni / Tikkanen, Ilkka / Lakkisto, Päivi / Paavola, Jere

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 662583

Abstract: Heart failure causes significant morbidity and mortality worldwide. The understanding of heart failure pathomechanisms and options for treatment remain incomplete. Zebrafish has proven useful for modeling human heart diseases due to similarity of ... ...

Abstract	Heart failure causes significant morbidity and mortality worldwide. The understanding of heart failure pathomechanisms and options for treatment remain incomplete. Zebrafish has proven useful for modeling human heart diseases due to similarity of zebrafish and mammalian hearts, fast easily tractable development, and readily available genetic methods. Embryonic cardiac development is rapid and cardiac function is easy to observe and quantify. Reverse genetics, by using morpholinos and CRISPR-Cas9 to modulate gene function, make zebrafish a primary animal model for
Language	English
Publishing date	2021-05-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.662583
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Article ; Online: Moderate hyperuricaemia ameliorated kidney damage in a low-renin model of experimental renal insufficiency.

Kurra, Venla / Eräranta, Arttu / Paavonen, Timo / Honkanen, Teemu / Myllymäki, Juhani / Riutta, Asko / Tikkanen, Ilkka / Lakkisto, Päivi / Mustonen, Jukka / Pörsti, Ilkka

Basic & clinical pharmacology & toxicology

2022 Volume 132, Issue 1, Page(s) 21–32

Abstract: Uric acid has promoted renal fibrosis and inflammation in experimental studies, but some studies have shown nephroprotective effects due to alleviated oxidative stress. We studied the influence of experimental hyperuricaemia in surgically 5/6 ... ...

Abstract	Uric acid has promoted renal fibrosis and inflammation in experimental studies, but some studies have shown nephroprotective effects due to alleviated oxidative stress. We studied the influence of experimental hyperuricaemia in surgically 5/6 nephrectomized rats. Three weeks after subtotal nephrectomy or sham operation, the rats were allocated to control diet or 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Then blood, urine and tissue samples were taken, and renal morphology and oxidative stress were examined. Inflammation and fibrosis were evaluated using immunohistochemistry and real-time PCR (RT-PCR). Remnant kidney rats ingesting normal or oxonic acid diet presented with ~60% reduction of creatinine clearance and suppressed plasma renin activity. Oxonic acid diet increased plasma uric acid levels by >80 μmol/L. In remnant kidney rats, moderate hyperuricaemia decreased glomerulosclerosis, tubulointerstitial damage and kidney mast cell count, without influencing the fibrosis marker collagen I messenger RNA (mRNA) content. In both sham-operated and 5/6 nephrectomized rats, the mast cell product 11-epi-prostaglandin-F
MeSH term(s)	Animals ; Rats ; Fibrosis ; Hyperuricemia/pathology ; Inflammation/pathology ; Kidney ; Kidney Diseases ; Nephrectomy ; Oxonic Acid/pharmacology ; Renal Insufficiency/pathology ; Renin/genetics ; Uric Acid
Chemical Substances	Oxonic Acid (5VT6420TIG) ; Renin (EC 3.4.23.15) ; Uric Acid (268B43MJ25)
Language	English
Publishing date	2022-10-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2134679-3
ISSN	1742-7843 ; 1742-7835
ISSN (online)	1742-7843
ISSN	1742-7835
DOI	10.1111/bcpt.13806
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Munuaisten denervaatio hypertension hoidossa.

Tikkanen, Ilkka / Lappalainen, Kimmo

Duodecim; laaketieteellinen aikakauskirja

2013 Volume 129, Issue 8, Page(s) 825–832

Abstract: Therapy resistant hypertension is common in hypertensive patients. The kidneys play an important role in the sympathetic nervous system overactivity associated with hypertension. Percutaneous transluminal ablation of renal nerves is a novel treatment ... ...

Title translation	Renal denervation in the treatment of hypertension.
Abstract	Therapy resistant hypertension is common in hypertensive patients. The kidneys play an important role in the sympathetic nervous system overactivity associated with hypertension. Percutaneous transluminal ablation of renal nerves is a novel treatment strategy for resistant hypertension decreasing both renal and systemic sympathetic activity. Renal denervation resulted in significant blood pressure reduction within 6 months in a multicentre, prospective, randomized trial. The treatment has proved safe and blood pressure reduction appears sustained up to 2 years. It also improves glycemic control. Further studies are needed to evaluate the mortality and morbidity impact of this promising therapy of resistant hypertension.
MeSH term(s)	Denervation/methods ; Female ; Humans ; Hypertension/surgery ; Kidney/innervation ; Male ; Prospective Studies ; Sympathetic Nervous System/physiopathology ; Sympathetic Nervous System/surgery ; Treatment Outcome
Language	Finnish
Publishing date	2013
Publishing country	Finland
Document type	English Abstract ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
ZDB-ID	127604-9
ISSN	0012-7183
ISSN	0012-7183
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Article ; Online: Potential role of sodium glucose cotransporter 2 inhibitors in the treatment of hypertension.

Tikkanen, Ilkka / Chilton, Robert / Johansen, Odd Erik

Current opinion in nephrology and hypertension

2016 Volume 25, Issue 2, Page(s) 81–86

Abstract: Purpose of review: The majority of patients with type 2 diabetes mellitus (T2DM) have hypertension requiring combination therapy. Sodium glucose cotransporter 2 (SGLT2) inhibitors are novel glucose-lowering drugs with shared and potentially unique ... ...

Abstract	Purpose of review: The majority of patients with type 2 diabetes mellitus (T2DM) have hypertension requiring combination therapy. Sodium glucose cotransporter 2 (SGLT2) inhibitors are novel glucose-lowering drugs with shared and potentially unique beneficial effects on cardiovascular risk beyond glycemic control. This review focuses on the potential role of SGLT2 inhibitors in the treatment of hypertension associated with T2DM. Recent findings: SGLT2 inhibitors reduce office SBP by 3-5 mmHg and DBP by 2-3 mmHg across all class members. Corresponding clinically meaningful, significant blood pressure (BP) lowering effects have been confirmed using 24 h ambulatory BP monitoring. SGLT2 inhibitors reduce BP irrespective of the type of background antihypertensive medication. The antihypertensive actions of SGLT2 inhibitors involve several mechanisms including modest diuretic effects, weight loss, and direct vascular effects leading to decreased arterial stiffness and vascular resistance. The first-in class cardiovascular outcome trial with empagliflozin showed a significant reduction in a composite endpoint of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction in T2DM patients at high risk for cardiovascular events. Summary: SGLT2 inhibitors have clinically significant antihypertensive effects. SGLT2 inhibition could be a potentially useful supplement to the BP-lowering treatment armamentarium in patients with T2DM.
MeSH term(s)	Benzhydryl Compounds/therapeutic use ; Blood Pressure/drug effects ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetic Angiopathies/drug therapy ; Diuretics ; Glucosides/therapeutic use ; Humans ; Hypertension/complications ; Hypertension/drug therapy ; Hypertension/metabolism ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Sodium-Glucose Transporter 2/antagonists & inhibitors ; Sodium-Glucose Transporter 2/metabolism ; Vascular Resistance/drug effects ; Weight Loss/drug effects
Chemical Substances	Benzhydryl Compounds ; Diuretics ; Glucosides ; Hypoglycemic Agents ; SLC5A2 protein, human ; Sodium-Glucose Transporter 2 ; empagliflozin (HDC1R2M35U)
Language	English
Publishing date	2016-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1151092-4
ISSN	1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
ISSN (online)	1473-6543 ; 1535-3842
ISSN	1062-4813 ; 1062-4821
DOI	10.1097/MNH.0000000000000199
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Article: Alterations of Cardiac Protein Kinases in Cyclic Nucleotide-Dependent Signaling Pathways in Human Ischemic Heart Failure.

Wang, Chunguang / Taskinen, Juuso H / Segersvärd, Heli / Immonen, Katariina / Kosonen, Riikka / Tolva, Johanna M / Mäyränpää, Mikko I / Kovanen, Petri T / Olkkonen, Vesa M / Sinisalo, Juha / Laine, Mika / Tikkanen, Ilkka / Lakkisto, Päivi

Frontiers in cardiovascular medicine

2022 Volume 9, Page(s) 919355

Abstract: Objectives: Impaired protein kinase signaling is a hallmark of ischemic heart disease (IHD). Inadequate understanding of the pathological mechanisms limits the development of therapeutic approaches. We aimed to identify the key cardiac kinases and ... ...

Abstract	Objectives: Impaired protein kinase signaling is a hallmark of ischemic heart disease (IHD). Inadequate understanding of the pathological mechanisms limits the development of therapeutic approaches. We aimed to identify the key cardiac kinases and signaling pathways in patients with IHD with an effort to discover potential therapeutic strategies. Methods: Cardiac kinase activity in IHD left ventricle (LV) and the related signaling pathways were investigated by kinomics, transcriptomics, proteomics, and integrated multi-omics approach. Results: Protein kinase A (PKA) and protein kinase G (PKG) ranked on top in the activity shift among the cardiac kinases. In the IHD LVs, PKA activity decreased markedly compared with that of controls (62% reduction, Conclusion: The deficiency in cAMP/PKA signaling pathway is strongly implicated in the pathogenesis of IHD. Natriuretic peptide CNP could be a potential therapeutic target for the modulation of cGMP/PKG signaling.
Language	English
Publishing date	2022-06-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2022.919355
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Article ; Online: Tankyrase Inhibition Attenuates Cardiac Dilatation and Dysfunction in Ischemic Heart Failure.

Wang, Hong / Segersvärd, Heli / Siren, Juuso / Perttunen, Sanni / Immonen, Katariina / Kosonen, Riikka / Chen, Yu-Chia / Tolva, Johanna / Laivuori, Mirjami / Mäyränpää, Mikko I / Kovanen, Petri T / Sinisalo, Juha / Laine, Mika / Tikkanen, Ilkka / Lakkisto, Päivi

International journal of molecular sciences

2022 Volume 23, Issue 17

Abstract: Hyperactive poly(ADP-ribose) polymerases (PARP) promote ischemic heart failure (IHF) after myocardial infarction (MI). However, the role of tankyrases (TNKSs), members of the PARP family, in pathogenesis of IHF remains unknown. We investigated the ... ...

Abstract	Hyperactive poly(ADP-ribose) polymerases (PARP) promote ischemic heart failure (IHF) after myocardial infarction (MI). However, the role of tankyrases (TNKSs), members of the PARP family, in pathogenesis of IHF remains unknown. We investigated the expression and activation of TNKSs in myocardium of IHF patients and MI rats. We explored the cardioprotective effect of TNKS inhibition in an isoproterenol-induced zebrafish HF model. In IHF patients, we observed elevated TNKS2 and DICER and concomitant upregulation of miR-34a-5p and miR-21-5p in non-infarcted myocardium. In a rat MI model, we found augmented TNKS2 and DICER in the border and infarct areas at the early stage of post-MI. We also observed consistently increased TNKS1 in the border and infarct areas and destabilized AXIN in the infarct area from 4 weeks onward, which in turn triggered Wnt/β-catenin signaling. In an isoproterenol-induced HF zebrafish model, inhibition of TNKS activity with XAV939, a TNKSs-specific inhibitor, protected against ventricular dilatation and cardiac dysfunction and abrogated overactivation of Wnt/β-catenin signaling and dysregulation of miR-34a-5p induced by isoproterenol. Our study unravels a potential role of TNKSs in the pathogenesis of IHF by regulating Wnt/β-catenin signaling and possibly modulating miRNAs and highlights the pharmacotherapeutic potential of TNKS inhibition for prevention of IHF.
MeSH term(s)	Animals ; Dilatation ; Heart Failure/drug therapy ; Isoproterenol/pharmacology ; MicroRNAs/genetics ; Rats ; Tankyrases/antagonists & inhibitors ; Tankyrases/metabolism ; Wnt Signaling Pathway ; Zebrafish/metabolism ; beta Catenin/metabolism
Chemical Substances	MIRN21 microRNA, zebrafish ; MicroRNAs ; beta Catenin ; mirn21 microRNA, rat ; Tankyrases (EC 2.4.2.30) ; Isoproterenol (L628TT009W)
Language	English
Publishing date	2022-09-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231710059
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Article ; Online: Unfavorable Reduction in the Ratio of Endothelin B to A Receptors in Experimental 5/6 Nephrectomy and Adenine Models of Chronic Renal Insufficiency.

Törmänen, Suvi / Lakkisto, Päivi / Eräranta, Arttu / Kööbi, Peeter / Tikkanen, Ilkka / Niemelä, Onni / Mustonen, Jukka / Pörsti, Ilkka

International journal of molecular sciences

2020 Volume 21, Issue 3

Abstract: Chronic renal insufficiency (CRI) is characterized by increased endothelin 1 (ET-1) synthesis. We studied rat kidney endothelin receptor A (ETA) and receptor B (ETB) expressions after 12 and 27 weeks of 5/6 nephrectomy, and after 12 weeks of 0.3% adenine ...

Abstract	Chronic renal insufficiency (CRI) is characterized by increased endothelin 1 (ET-1) synthesis. We studied rat kidney endothelin receptor A (ETA) and receptor B (ETB) expressions after 12 and 27 weeks of 5/6 nephrectomy, and after 12 weeks of 0.3% adenine diet, representing proteinuric and interstitial inflammation models of CRI, respectively. Uric acid and calcium-phosphate metabolism were modulated after 5/6 nephrectomy, while ETA blocker and calcimimetic were given with adenine. Endothelin receptor mRNA levels were measured using RT-qPCR and protein levels using autoradiography (5/6 nephrectomy) or ELISA (adenine model). Both 12 and 27 weeks after 5/6 nephrectomy, kidney cortex ETA protein was increased by ~60% without changes in ETB protein, and the ETB:ETA ratio was reduced. However, the ETB:ETA mRNA ratio did not change. In the adenine model, kidney ETA protein was reduced by ~70%, while ETB protein was suppressed by ~95%, and the ETB:ETA ratio was reduced by ~85%, both at the protein and mRNA levels. The additional interventions did not influence the observed reductions in the ETB:ETA ratio. To conclude, unfavorable reduction in the ETB:ETA protein ratio was observed in two different models of CRI. Therefore, ETA blockade may be beneficial in a range of diseases that cause impaired kidney function.
MeSH term(s)	Adenine/adverse effects ; Animals ; Calcium/metabolism ; Disease Models, Animal ; Gene Expression Regulation/drug effects ; Kidney Cortex/metabolism ; Male ; Nephrectomy/adverse effects ; Phosphates/metabolism ; Rats ; Receptor, Endothelin A/genetics ; Receptor, Endothelin A/metabolism ; Receptor, Endothelin B/genetics ; Receptor, Endothelin B/metabolism ; Renal Insufficiency, Chronic/chemically induced ; Renal Insufficiency, Chronic/genetics ; Renal Insufficiency, Chronic/metabolism ; Uric Acid/metabolism
Chemical Substances	Phosphates ; Receptor, Endothelin A ; Receptor, Endothelin B ; ednrb protein, rat ; Uric Acid (268B43MJ25) ; Adenine (JAC85A2161) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2020-01-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21030936
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