Oxidant Stress-induced Protein Thiyl Radical Is Associated To Enhancement Of Complex I S-glutathionylation In The Enos(-/-) Murine Heart
Cardiovascular System & Cardiology; Mitochondria; Myocardium; nitric-oxide synthase; Redox; Super oxide
Kang P T; Chen C L; Chen Y R
Circulation
2012
2012-11
Journal Article or Conference Abstract Publication
n/a
Role of angiotensin II in sympathetic nervous system induced left ventricular dysfunction
contractility; Physiology; myocardium; Pharmacology & Pharmacy; nitric-oxide; catecholamines; inhibitors; mechanisms; hearts; rabbits; bradykinin; attenuation; calcium channel opener-blocker; captopril; converting-enzyme inhibitor; myocardial; nifedipine; ramiprilat
Experiments were undertaken to determine whether angiotensin (Ang) II concentration increases during massive sympathetic nervous system (SNS) activation and whether such an increase plays a role in the pathogenesis of SNS-induced left ventricular (LV) dysfunction. We also sought to determine whether excessive Ca2+ uptake through L-type channels due to intense adrenoceptor activation is responsible for the LV dysfunction. AngII concentration was measured in the plasma and myocardium before and after massively activating the SNS with an intracisternal injection of veratrine. In separate experiments, rabbits were given losartan, enalaprilat, enalaprilat plus HOE-140, nifedipine, betaBay K 4866, or saline before massively activating the SNS. LV function was evaluated 2.5 h later. The intense SNS activity caused plasma and myocardial AngII to increase by 400 and 437%, respectively. AngII receptor blockade did not prevent LV dysfunction. In contrast, enalaprilat reduced the degree of dysfunction, but its cardioprotection was abolished by HOE-140. Although nifedipine prevented SNS-induced LV dysfunction, administration of the Ca2+ channel opener, betaBay K 4866, did not increase its severity. Our results indicate that AngII is not involved in the pathogenesis of SNS-induced LV dysfunction and that the cardioprotection provided by angiotensin converting enzyme (ACE) inhibition is due to activation of a bradykinin pathway. Furthermore, the finding that the magnitude of the LV dysfunction was reduced by enalaprilat, and not increased by betaBay K 4866, suggests that intense adrenoceptor activation of L-type Ca2+ channels is not the primary pathogenetic mechanism.
Bosso F J; Jarjoura D G; Pilati C F
Canadian Journal of Physiology and Pharmacology
1999
1999-10
Journal Article or Conference Abstract Publication
n/a
Myocardial CXCR4 expression is required for mesenchymal stem cell mediated repair following acute myocardial infarction.
Mice; Myocardium; Cells; Receptors; Proteins; Animal Studies; Cell Physiology; Cardiovascular System Physiology; Myocardial Infarction; Myocardial Infarction – Therapy; Stem Cells – Metabolism; Cytokines – Metabolism; Cell Surface – Metabolism; Myocardial Infarction – Pathology; Apoptosis – Physiology; Cell Movement – Physiology; Cell Surface; Coronary Circulation – Physiology; Gene Expression – Physiology; Stem Cells – Transplantation
BACKGROUND: Overexpression of stromal cell-derived factor-1 in injured tissue leads to improved end-organ function. In this study, we quantify the local trophic effects of mesenchymal stem cell (MSC) stromal cell-derived factor-1 release on the effects of MSC engraftment in the myocardium after acute myocardial infarction. METHODS AND RESULTS: Conditional cardiac myocyte CXCR4 (CM-CXCR4) null mice were generated by use of tamoxifen-inducible cardiac-specific cre by crossing CXCR4 floxed with MCM-cre mouse. Studies were performed in littermates with (CM-CXCR4 null) or without (control) tamoxifen injection 3 weeks before acute myocardial infarction. One day after acute myocardial infarction, mice received 100 000 MSC or saline via tail vein. We show [alpha]-myosin heavy chain MerCreMer and the MLC-2v promoters are active in cardiac progenitor cells. MSC engraftment in wild-type mice decreased terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling positive CM (-44%, P\textless0.01), increased cardiac progenitor cell recruitment (100.9%, P\textless0.01), and increased cardiac myosin-positive area (39%, P\textless0.05) at 4, 7, and 21 days after acute myocardial infarction, respectively. MSC in wild-type mice resulted in 107.4% (P\textless0.05) increase in ejection fraction in comparison with 25.9% (P=NS) increase in CM-CXCR4 null mice. These differences occurred despite equivalent increases (16%) in vascular density in response to MSC infusion in wild-type and CM-CXCR4 null mice. CONCLUSIONS: These data demonstrate that the local trophic effects of MSC require cardiac progenitor cell and CM-CXCR4 expression and are mediated by MSC stromal cell-derived factor-1 secretion. Our results further demonstrate and quantify for the first time a specific paracrine mechanism of MSC engraftment. In the absence of CM-CXCR4 expression, there is a significant loss of functional benefit in MSC-mediated repair despite equal increases in vascular density.
Dong F; Harvey J; Finan A; Weber K; Agarwal U; Penn M S
Circulation
2012
2012-07-17
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1161/circulationaha.111.082453" target="_blank" rel="noreferrer noopener">10.1161/circulationaha.111.082453</a>
Apolipoprotein A1 regulates coenzyme Q10 absorption, mitochondrial function, and infarct size in a mouse model of myocardial infarction.
Male; Animals; Mice; Myocardium; Lipid Metabolism; Mitochondria; Heart/drug effects; Antioxidants/administration & dosage/*metabolism/pharmacokinetics/therapeutic use; Apolipoprotein A-I/blood/genetics/*metabolism; Cardiotonic Agents/administration & dosage/metabolism/pharmacokinetics/therapeutic use; Dietary Supplements; Electron Transport Complex II/chemistry/metabolism; Electron Transport Complex III/chemistry/metabolism; Electron Transport/drug effects; Hypoalphalipoproteinemias/physiopathology; Intestinal Absorption; Myocardial Infarction/etiology/metabolism/pathology/*therapy; Myocardial Reperfusion Injury/blood/metabolism/pathology/prevention & control; Myocardium/enzymology/*metabolism/pathology; Tissue Distribution; Ubiquinone/administration & dosage/*analogs & derivatives/metabolism/pharmacokinetics/therapeutic use; Injections; Biological; Models; Animal; Knockout; Intraperitoneal; *Disease Models; Heart/drug effects/enzymology/*metabolism; Proteins; Animal Studies; Apolipoproteins; Coenzyme Q; Proteins – Metabolism; Heart – Drug Effects; Myocardial Infarction – Therapy; Apolipoproteins – Blood; Apolipoproteins – Metabolism; Antioxidants – Administration and Dosage; Antioxidants – Metabolism; Antioxidants – Pharmacokinetics; Antioxidants – Therapeutic Use; Cardiotonic Agents – Administration and Dosage; Cardiotonic Agents – Metabolism; Cardiotonic Agents – Pharmacokinetics; Cardiotonic Agents – Therapeutic Use; Coenzyme Q – Administration and Dosage; Coenzyme Q – Metabolism; Coenzyme Q – Pharmacokinetics; Coenzyme Q – Therapeutic Use; Electron Transport – Drug Effects; Inborn Errors – Physiopathology; Mitochondria – Drug Effects; Mitochondria – Metabolism; Myocardial Infarction – Etiology; Myocardial Infarction – Metabolism; Myocardial Infarction – Pathology; Myocardial Reperfusion Injury – Blood; Myocardial Reperfusion Injury – Metabolism; Myocardial Reperfusion Injury – Pathology; Myocardial Reperfusion Injury – Prevention and Control; Myocardium – Metabolism; Myocardium – Pathology
HDL and apolipoprotein A1 (apoA1) concentrations inversely correlate with risk of death from ischemic heart disease; however, the role of apoA1 in the myocardial response to ischemia has not been well defined. To test whether apoA1, the primary HDL apolipoprotein, has an acute anti-inflammatory role in ischemic heart disease, we induced myocardial infarction via direct left anterior descending coronary artery ligation in apoA1 null (apoA1(-/-)) and apoA1 heterozygous (apoA1(+/-)) mice. We observed that apoA1(+/-) and apoA1(-/-) mice had a 52% and 125% increase in infarct size as a percentage of area at risk, respectively, compared with wild-type (WT) C57BL/6 mice. Mitochondrial oxidation contributes to tissue damage in ischemia-reperfusion injury. A substantial defect was present at baseline in the electron transport chain of cardiac myocytes from apoA1(-/-) mice localized to the coenzyme Q (CoQ) pool with impaired electron transfer (67% decrease) from complex II to complex III. Administration of coenzyme Q10 (CoQ10) to apoA1 null mice normalized the cardiac mitochondrial CoQ pool and reduced infarct size to that observed in WT mice. CoQ10 administration did not significantly alter infarct size in WT mice. These data identify CoQ pool content leading to impaired mitochondrial function as major contributors to infarct size in the setting of low HDL/apoA1. These data suggest a previously unappreciated mechanism for myocardial stunning, cardiac dysfunction, and muscle pain associated with low HDL and low apoA1 concentrations that can be corrected by CoQ10 supplementation and suggest populations of patients that may benefit particularly from CoQ10 supplementation.
Dadabayev Alisher R; Yin Guotian; Latchoumycandane Calivarathan; McIntyre Thomas M; Lesnefsky Edward J; Penn Marc S
The Journal of nutrition
2014
2014-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3945/jn.113.184291" target="_blank" rel="noreferrer noopener">10.3945/jn.113.184291</a>
AMP-activated kinase "Keaps" ischemia/reperfusion-induced necroptosis under control.
*AMP-Activated Protein Kinases; *AMPK; *Apoptosis; *Ischemia/reperfusion; *Myocardium; *Necroptosis; *Necrosis; Apoptosis; Humans; Myocardial Reperfusion Injury; Myocardium
Kanugula Anantha K; Thodeti Charles K
International journal of cardiology
2018
2018-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.ijcard.2018.02.053" target="_blank" rel="noreferrer noopener">10.1016/j.ijcard.2018.02.053</a>