Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Excess ischemic tachyarrhythmias trigger protection against myocardial infarction in hypertensive rats

J. Neckář, P. Alánová, V. Olejníčková, F. Papoušek, L. Hejnová, J. Šilhavý, M. Behuliak, M. Bencze, J. Hrdlička, M. Vecka, D. Jarkovská, J. Švíglerová, E. Mistrová, M. Štengl, J. Novotný, B. Ošťádal, M. Pravenec, F. Kolář

. 2021 ; 135 (17) : 2143-2163. [pub] 20210917

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc22003707

Increased level of C-reactive protein (CRP) is a risk factor for cardiovascular diseases, including myocardial infarction and hypertension. Here, we analyzed the effects of CRP overexpression on cardiac susceptibility to ischemia/reperfusion (I/R) injury in adult spontaneously hypertensive rats (SHR) expressing human CRP transgene (SHR-CRP). Using an in vivo model of coronary artery occlusion, we found that transgenic expression of CRP predisposed SHR-CRP to repeated and prolonged ventricular tachyarrhythmias. Excessive ischemic arrhythmias in SHR-CRP led to a significant reduction in infarct size (IS) compared with SHR. The proarrhythmic phenotype in SHR-CRP was associated with altered heart and plasma eicosanoids, myocardial composition of fatty acids (FAs) in phospholipids, and autonomic nervous system imbalance before ischemia. To explain unexpected IS-limiting effect in SHR-CRP, we performed metabolomic analysis of plasma before and after ischemia. We also determined cardiac ischemic tolerance in hearts subjected to remote ischemic perconditioning (RIPer) and in hearts ex vivo. Acute ischemia in SHR-CRP markedly increased plasma levels of multiple potent cardioprotective molecules that could reduce IS at reperfusion. RIPer provided IS-limiting effect in SHR that was comparable with myocardial infarction observed in naïve SHR-CRP. In hearts ex vivo, IS did not differ between the strains, suggesting that extra-cardiac factors play a crucial role in protection. Our study shows that transgenic expression of human CRP predisposes SHR-CRP to excess ischemic ventricular tachyarrhythmias associated with a drop of pump function that triggers myocardial salvage against lethal I/R injury likely mediated by protective substances released to blood from hypoxic organs and tissue at reperfusion.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22003707
003      
CZ-PrNML
005      
20250618084741.0
007      
ta
008      
220113s2021 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1042/CS20210648 $2 doi
035    __
$a (PubMed)34486670
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Neckář, Jan $u Laboratory of Developmental Cardiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic $u Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
245    10
$a Excess ischemic tachyarrhythmias trigger protection against myocardial infarction in hypertensive rats / $c J. Neckář, P. Alánová, V. Olejníčková, F. Papoušek, L. Hejnová, J. Šilhavý, M. Behuliak, M. Bencze, J. Hrdlička, M. Vecka, D. Jarkovská, J. Švíglerová, E. Mistrová, M. Štengl, J. Novotný, B. Ošťádal, M. Pravenec, F. Kolář
520    9_
$a Increased level of C-reactive protein (CRP) is a risk factor for cardiovascular diseases, including myocardial infarction and hypertension. Here, we analyzed the effects of CRP overexpression on cardiac susceptibility to ischemia/reperfusion (I/R) injury in adult spontaneously hypertensive rats (SHR) expressing human CRP transgene (SHR-CRP). Using an in vivo model of coronary artery occlusion, we found that transgenic expression of CRP predisposed SHR-CRP to repeated and prolonged ventricular tachyarrhythmias. Excessive ischemic arrhythmias in SHR-CRP led to a significant reduction in infarct size (IS) compared with SHR. The proarrhythmic phenotype in SHR-CRP was associated with altered heart and plasma eicosanoids, myocardial composition of fatty acids (FAs) in phospholipids, and autonomic nervous system imbalance before ischemia. To explain unexpected IS-limiting effect in SHR-CRP, we performed metabolomic analysis of plasma before and after ischemia. We also determined cardiac ischemic tolerance in hearts subjected to remote ischemic perconditioning (RIPer) and in hearts ex vivo. Acute ischemia in SHR-CRP markedly increased plasma levels of multiple potent cardioprotective molecules that could reduce IS at reperfusion. RIPer provided IS-limiting effect in SHR that was comparable with myocardial infarction observed in naïve SHR-CRP. In hearts ex vivo, IS did not differ between the strains, suggesting that extra-cardiac factors play a crucial role in protection. Our study shows that transgenic expression of human CRP predisposes SHR-CRP to excess ischemic ventricular tachyarrhythmias associated with a drop of pump function that triggers myocardial salvage against lethal I/R injury likely mediated by protective substances released to blood from hypoxic organs and tissue at reperfusion.
650    _2
$a akční potenciály $7 D000200
650    _2
$a zvířata $7 D000818
650    _2
$a krevní tlak $7 D001794
650    _2
$a C-reaktivní protein $x genetika $x metabolismus $7 D002097
650    _2
$a modely nemocí na zvířatech $7 D004195
650    _2
$a srdeční frekvence $7 D006339
650    _2
$a lidé $7 D006801
650    _2
$a hypertenze $x komplikace $x metabolismus $x patofyziologie $7 D006973
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a reperfuzní poškození myokardu $x etiologie $x metabolismus $x patofyziologie $x prevence a kontrola $7 D015428
650    _2
$a myokard $x metabolismus $x patologie $7 D009206
650    _2
$a potkani inbrední SHR $7 D011918
650    _2
$a potkani transgenní $7 D055647
650    _2
$a komorová tachykardie $x etiologie $x metabolismus $x patofyziologie $7 D017180
650    _2
$a fibrilace komor $x etiologie $x metabolismus $x patofyziologie $7 D014693
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Alánová, Petra $u Laboratory of Developmental Cardiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Olejníčková, Veronika $u Laboratory of Developmental Cardiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic $u Institute of Anatomy, First Faculty of Medicine, Charles University, Prague, Czech Republic
700    1_
$a Papoušek, František $u Laboratory of Developmental Cardiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Hejnová, Lucie $u Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic
700    1_
$a Šilhavý, Jan $u Laboratory of Genetics of Model Diseases, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Behuliak, Michal $u Laboratory of Experimental Hypertension, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic $7 xx0196023
700    1_
$a Bencze, Michal $u Laboratory of Experimental Hypertension, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Hrdlička, Jaroslav $u Laboratory of Developmental Cardiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Vecka, Marek $u 4th Department of Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic
700    1_
$a Jarkovská, Dagmar $u Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic
700    1_
$a Švíglerová, Jitka $u Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic
700    1_
$a Mistrová, Eliška $u Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic
700    1_
$a Štengl, Milan $u Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic
700    1_
$a Novotný, Jiří $u Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic
700    1_
$a Ošťádal, Bohuslav $u Laboratory of Developmental Cardiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Pravenec, Michal $u Laboratory of Genetics of Model Diseases, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Kolář, František $u Laboratory of Developmental Cardiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
773    0_
$w MED00009494 $t Clinical science (1979) $x 1470-8736 $g Roč. 135, č. 17 (2021), s. 2143-2163
856    41
$u https://pubmed.ncbi.nlm.nih.gov/34486670 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220113 $b ABA008
991    __
$a 20250618084732 $b ABA008
999    __
$a ok $b bmc $g 1751229 $s 1154856
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 135 $c 17 $d 2143-2163 $e 20210917 $i 1470-8736 $m Clinical science (1979) $n Clin Sci (Lond) $x MED00009494
LZP    __
$a Pubmed-20220113

Find record

Citation metrics

Archiving options