@article{MTMT:3297273,
	title = {Traumatic brain injury impairs myogenic constriction of cerebral arteries: role of mitochondria-derived H2O2 and TRPV4-dependent activation of BKCa channels},
	url = {https://m2.mtmt.hu/api/publication/3297273},
	author = {Szarka, Nikolett and Pabbidi, MR and Amrein, Krisztina and Czeiter, Endre and Berta, Gergely and Pohóczky, Krisztina and Helyes, Zsuzsanna and Ungvári, Zoltán István and Koller, Ákos and Büki, András and Tóth, Péter József},
	doi = {10.1089/neu.2017.5056},
	journal-iso = {J NEUROTRAUM},
	journal = {JOURNAL OF NEUROTRAUMA},
	volume = {35},
	unique-id = {3297273},
	issn = {0897-7151},
	abstract = {Traumatic brain injury (TBI) impairs autoregulation of cerebral blood flow, which contributes to the development of secondary brain injury increasing mortality of patients. Impairment of pressure-induced myogenic constriction of cerebral arteries plays a critical role in autoregulatory dysfunction; however, the underlying cellular and molecular mechanisms are not well understood. To determine the role of mitochondria-derived H2O2 and large-conductance calcium-activated potassium channels (BKCa) in myogenic autoregulatory dysfunction, middle cerebral arteries (MCAs) were isolated from rats with severe weight drop-impact acceleration brain injury (24 h post-impact). We found that post-TBI MCAs exhibited impaired myogenic constriction, which was restored by treatment with a mitochondria-targeted antioxidant (mitoTEMPO), by scavenging of H2O2 (PEG-catalase) and by blocking both BKCa channels (paxilline) and TRPV4 channels (HC067047). Further, exogenous administration of H2O2 elicited significant dilation of MCAs, which was inhibited by blocking either BKCa or TRPV4 channels. Vasodilation induced by the TRPV4 agonist GSK1016790A was inhibited by paxilline. In cultured vascular smooth muscle cells H2O2 activated BKCa currents, which were inhibited by blockade of TRPV4 channels. Collectively, our results suggest that after TBI excessive mitochondria-derived H2O2 activates BKCa channels via a TRPV4-dependent pathway in the vascular smooth muscle cells, which impairs pressure-induced constriction of cerebral arteries. Future studies should elucidate the therapeutic potential of pharmacological targeting of this pathway in TBI to restore autoregulatory function in order to prevent secondary brain damage and decrease mortality.},
	keywords = {BLOOD-FLOW; ENDOTHELIAL-CELLS; AUTO-REGULATION; POTASSIUM CHANNELS; HYDROGEN-PEROXIDE; SMOOTH-MUSCLE-CELLS; AUTOREGULATION; resistance arteries; HEAD-INJURY; Intracranial Hypertension; Clinical Neurology; Critical Care Medicine; Oxidative stress; Oxidative stress},
	year = {2018},
	eissn = {1557-9042},
	pages = {930-939},
	orcid-numbers = {Czeiter, Endre/0000-0002-9578-6944; Pohóczky, Krisztina/0000-0003-0385-5162; Ungvári, Zoltán István/0000-0002-6035-6039; Koller, Ákos/0000-0003-3256-8701}
}

@article{MTMT:3367042,
	title = {Treatment with the mitochondrial-targeted antioxidant peptide SS-31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice},
	url = {https://m2.mtmt.hu/api/publication/3367042},
	author = {Tarantini, Stefano and Valcarcel-Ares, NM and Yabluchanskiy, A and Fülöp, Gábor Áron and Hertelendy, Péter and Gautam, T and Farkas, Eszter and Perz, A and Rabinovitch, PS and Sonntag, WE and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1111/acel.12731},
	journal-iso = {AGING CELL},
	journal = {AGING CELL},
	volume = {17},
	unique-id = {3367042},
	issn = {1474-9718},
	year = {2018},
	eissn = {1474-9726},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Farkas, Eszter/0000-0002-8478-9664; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:3195505,
	title = {HYPERTENSION-INDUCED ENHANCED MYOGENIC CONSTRICTION OF CEREBRAL ARTERIES IS PRESERVED AFTER TRAUMATIC BRAIN INJURY.},
	url = {https://m2.mtmt.hu/api/publication/3195505},
	author = {Szarka, Nikolett and Amrein, Krisztina and Horváth, Péter and Ivic, Ivan and Czeiter, Endre and Büki, András and Koller, Ákos and Tóth, Péter József},
	doi = {10.1089/neu.2016.4962},
	journal-iso = {J NEUROTRAUM},
	journal = {JOURNAL OF NEUROTRAUMA},
	volume = {34},
	unique-id = {3195505},
	issn = {0897-7151},
	abstract = {Traumatic brain injury (TBI) was shown to impair pressure-induced myogenic response of cerebral arteries, which is associated with vascular and neural dysfunction and increased mortality of TBI patients. Hypertension was shown to enhance myogenic tone of cerebral arteries via increased vascular production of 20-hydroxyeicosatrienoic acid (HETE). This adaptive mechanism protects brain tissue form pressure/volume overload, but it can also lead to increased susceptibility to cerebral ischemia. Although both effects may potentiate the detrimental vascular consequences of TBI, it is not known how hypertension modulates the effect of TBI on myogenic responses of cerebral vessels. We hypothesized that in hypertensive rats, the enhanced myogenic cerebrovascular response is preserved after TBI. Thus, we investigated the myogenic responses of isolated middle cerebral arteries (MCA) of normotensive and spontaneously hypertensive rats (SHR) after severe impact acceleration diffuse brain injury. TBI diminished myogenic constriction of MCAs isolated from normotensive rats, whereas the 20-HETE-mediated enhanced myogenic response of MCAs isolated from SHRs was not affected by TBI. These results suggest that the optimal cerebral perfusion pressure values and vascular signaling pathways can be different and thus should be targeted differently in normotensive and hypertensive patients following TBI.},
	keywords = {BLOOD-FLOW; INHIBITOR; CA2+; RATS; EPIDEMIOLOGY; AUTOREGULATION; AUTOREGULATION; cerebral blood flow; Clinical Neurology; Critical Care Medicine; 20-HETE; 20-HETE; SEVERE HEAD-INJURY; Oxidative stress},
	year = {2017},
	eissn = {1557-9042},
	pages = {2315-2319},
	orcid-numbers = {Czeiter, Endre/0000-0002-9578-6944; Koller, Ákos/0000-0003-3256-8701}
}

@article{MTMT:3110623,
	title = {Traumatic brain injury-induced autoregulatory dysfunction and spreading depression-related neurovascular uncoupling: Pathomechanisms, perspectives, and therapeutic implications},
	url = {https://m2.mtmt.hu/api/publication/3110623},
	author = {Tóth, Péter József and Szarka, Nikolett and Farkas, Eszter and Ezer, Erzsébet and Czeiter, Endre and Amrein, Krisztina and Ungvári, Zoltán István and Hartings, JA and Büki, András and Koller, Ákos},
	doi = {10.1152/ajpheart.00267.2016},
	journal-iso = {AM J PHYSIOL HEART C},
	journal = {AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY},
	volume = {311},
	unique-id = {3110623},
	issn = {0363-6135},
	year = {2016},
	eissn = {1522-1539},
	pages = {H1118-H1131},
	orcid-numbers = {Farkas, Eszter/0000-0002-8478-9664; Czeiter, Endre/0000-0002-9578-6944; Ungvári, Zoltán István/0000-0002-6035-6039; Koller, Ákos/0000-0003-3256-8701}
}

@article{MTMT:2798902,
	title = {Aging exacerbates pressure-induced mitochondrial oxidative stress in mouse cerebral arteries},
	url = {https://m2.mtmt.hu/api/publication/2798902},
	author = {Springó, Zsolt and Tarantini, Stefano and Tóth, Péter József and Tucsek, Z and Koller, Ákos and Sonntag, WE and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1093/gerona/glu244},
	journal-iso = {J GERONTOL A-BIOL MED SCI},
	journal = {JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES},
	volume = {70},
	unique-id = {2798902},
	issn = {1079-5006},
	abstract = {Epidemiological studies demonstrate that in addition to the increased prevalence of hypertension in old patients, the deleterious cerebrovascular effects of hypertension ( including atherosclerosis, stroke, and vascular cognitive impairment) are also exacerbated in elderly individuals. The cellular mechanisms by which aging and hypertension interact to promote cerebrovascular pathologies are not well understood. To test the hypothesis that aging exacerbates high pressure-induced mitochondrial oxidative stress, we exposed isolated segments of the middle cerebral arteries of young ( 3 months) and aged ( 24 months) C57BL/6 mice to 60 or 140 mmHg intraluminal pressure and assessed changes in mitochondrial reactive oxygen species production using a mitochondria-targeted redox-sensitive fluorescent indicator dye ( MitoSox) by confocal microscopy. Perinuclear MitoSox fluorescence was significantly stronger in high pressure-exposed middle cerebral arteries compared with middle cerebral arteries of the same animals exposed to 60 mmHg, indicating that high pressure increases mitochondrial reactive oxygen species production in the smooth muscle cells of cerebral arteries. Comparison of young and aged middle cerebral arteries showed that aging exacerbates high pressure-induced mitochondrial reactive oxygen species production in cerebral arteries. We propose that increased mechanosensitive mitochondrial oxidative stress may potentially exacerbate cerebrovascular injury and vascular inflammation in aging.},
	keywords = {ALZHEIMERS-DISEASE; HYPERTENSION; mitochondrion; SMOOTH-MUSCLE-CELLS; middle cerebral artery; Geriatrics & Gerontology; SECRETORY PHENOTYPE; NAD(P)H OXIDASE; CEREBROMICROVASCULAR ENDOTHELIAL-CELLS; IMPAIRS ANGIOGENIC CAPACITY; BETA-AMYLOID GENERATION; SUPEROXIDE-PRODUCTION; ACUTE HYPERTENSION; Oxidative stress},
	year = {2015},
	eissn = {1758-535X},
	pages = {1355-1359},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Koller, Ákos/0000-0003-3256-8701; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:2496231,
	title = {Resveratrol treatment rescues neurovascular coupling in aged mice: role of improved cerebromicrovascular endothelial function and downregulation of NADPH oxidase},
	url = {https://m2.mtmt.hu/api/publication/2496231},
	author = {Tóth, Péter József and Tarantini, Stefano and Tucsek, Zsuzsanna and Ashpole, NM and Sosnowska, D and Gautam, T and Ballabh, P and Koller, Ákos and Sonntag, WE and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1152/ajpheart.00744.2013},
	journal-iso = {AM J PHYSIOL HEART C},
	journal = {AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY},
	volume = {306},
	unique-id = {2496231},
	issn = {0363-6135},
	abstract = {Moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is essential for the maintenance of normal neuronal function. Increased oxidative stress that occurs with aging was shown to impair neurovascular coupling, which likely contributes to a significant age-related decline in higher brain function, increasing the risk for vascular cognitive impairment (VCI). Resveratrol is a polyphenolic compound that exerts significant anti-aging protective effects in large vessels but its effects on the cerebromicrovasculature remain poorly defined. The present study was undertaken to investigate the capacity of resveratrol to improve neurovascular coupling in aging. In aged (24 months old) C57BL/6 mice L-NAME sensitive, NO-mediated CBF responses to whisker stimulation and to the endothelium-dependent dilator acethylcholine (ACh) were impaired as compared to those in young (3 months old) mice. Treatment of aged mice with resveratrol rescued neurovascular coupling and ACh-induced responses, which was associated with down-regulation of cortical expression of NADPH oxidase and decreased levels of biomarkers of oxidative/nitrative stress (3-nitrotyrosine, 8-isoprostanes). Resveratrol also attenuated age-related increases in ROS production in cultured cerebromicrovascular endothelial cells (DCF fluorescence, flow cytometry). In conclusion, treatment with resveratrol rescues cortical neurovascular coupling responses to increased neuronal activity in aged mice, likely by restoring cerebromicrovascular endothelial function via down-regulation of NADPH-oxidase derived ROS production. Beneficial cerebromicrovascular effects of resveratrol likely contribute to its protective effects on higher brain function in aging.},
	year = {2014},
	eissn = {1522-1539},
	pages = {H299-H308},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Koller, Ákos/0000-0003-3256-8701; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:2528667,
	title = {Role of mitochondrial oxidative stress in hypertension},
	url = {https://m2.mtmt.hu/api/publication/2528667},
	author = {Dikalov, SI and Ungvári, Zoltán István},
	doi = {10.1152/ajpheart.00089.2013},
	journal-iso = {AM J PHYSIOL HEART C},
	journal = {AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY},
	volume = {305},
	unique-id = {2528667},
	issn = {0363-6135},
	year = {2013},
	eissn = {1522-1539},
	pages = {H1417-H1427},
	orcid-numbers = {Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:2528682,
	title = {Mitochondria and Cardiovascular Aging},
	url = {https://m2.mtmt.hu/api/publication/2528682},
	author = {Dai, DF and Rabinovitch, PS and Ungvári, Zoltán István},
	doi = {10.1161/CIRCRESAHA.111.246140},
	journal-iso = {CIRC RES},
	journal = {CIRCULATION RESEARCH},
	volume = {110},
	unique-id = {2528682},
	issn = {0009-7330},
	year = {2012},
	eissn = {1524-4571},
	pages = {1109-1124},
	orcid-numbers = {Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:1416573,
	title = {Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice},
	url = {https://m2.mtmt.hu/api/publication/1416573},
	author = {Csiszar, Anna and Labinskyy, N and Perez, V and Recchia, FA and Podlutsky, A and Mukhopadhyay, P and Losonczy, György and Pacher, Pál and Austad, SN and Bartke, A and Ungvári, Zoltán István},
	doi = {10.1152/ajpheart.412.2008},
	journal-iso = {AM J PHYSIOL HEART C},
	journal = {AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY},
	volume = {295},
	unique-id = {1416573},
	issn = {0363-6135},
	abstract = {Csiszar A, Labinskyy N, Perez V, Recchia FA, Podlutsky A, Mukhopadhyay P, Losonczy G, Pacher P, Austad SN, Bartke A, Ungvari Z. Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice. Am J Physiol Heart Circ Physiol 295: H1882-H1894, 2008. First published August 29, 2008; doi:10.1152/ajpheart.412.2008. - Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O-2(center dot-) and H2O2 production, mitochondrial reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and nitric oxide (NO) production in aortas of Ames dwarf and wild-type control mice. In Ames dwarf aortas endothelial O-2(center dot-) and H2O2 production and ROS generation by mitochondria were enhanced compared with those in vessels of wild-type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu, Zn-SOD, glutathione peroxidase (GPx)-1, and endothelial nitric oxide synthase (eNOS). NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild-type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O-2(center dot-) and H2O2 production and ROS generation by mitochondria and upregulated expression of Mn-SOD, Cu, Zn-SOD, GPx-1, and eNOS. Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress.},
	keywords = {LIFE-SPAN; ATHEROSCLEROSIS; NITRIC-OXIDE; VENTRICULAR MYOCYTES; Caloric Restriction; vascular disease; GROWTH-FACTOR-I; CONTRACTILE DYSFUNCTION; HORMONE RECEPTOR KNOCKOUT; CARDIAC-SPECIFIC OVEREXPRESSION; Prop1(df/df) mice; NAKED MOLE-RAT; MITOCHONDRIAL SUPEROXIDE-PRODUCTION; senescence},
	year = {2008},
	eissn = {1522-1539},
	pages = {H1882-H1894},
	orcid-numbers = {Losonczy, György/0000-0002-5340-360X; Pacher, Pál/0000-0001-7036-8108; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:1151559,
	title = {Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of vasodilator prostanoids},
	url = {https://m2.mtmt.hu/api/publication/1151559},
	author = {Hortobagyi, L and Kis, B and Hrabák, András and Horváth, Béla András and Huszty, Gergely and Schweer, H and Benyó, Balázs István and Sándor, Péter and Busija, DW and Benyó, Zoltán},
	doi = {10.1016/j.brainres.2006.11.009},
	journal-iso = {BRAIN RES},
	journal = {BRAIN RESEARCH},
	volume = {1131},
	unique-id = {1151559},
	issn = {0006-8993},
	year = {2007},
	eissn = {1872-6240},
	pages = {129-137},
	orcid-numbers = {Hrabák, András/0000-0002-7818-6509; Benyó, Balázs István/0000-0003-2770-9127; Sándor, Péter/0000-0002-1257-8235; Benyó, Zoltán/0000-0001-6015-0359}
}