scholarly journals Effects of Heme Oxygenase-1 Upregulation on Blood Pressure and Cardiac Function in an Animal Model of Hypertensive Myocardial Infarction

2013 ◽  
Vol 14 (2) ◽  
pp. 2684-2706 ◽  
Author(s):  
Tian-meng Chen ◽  
Jian Li ◽  
Lin Liu ◽  
Li Fan ◽  
Xiao-ying Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Blood Pressure ◽  
Animal Model ◽  
Cardiac Function ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

Abstract 648: Heme-oxygenase-1 Gene Expression Ameliorates Cardiac Dysfunction Following Myocardial Infarction In C57 Mice By Recruitment Of Angiogenic Factors And Angiogenesis In C57 Mice

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
David Sacerdoti ◽  
Sumit R Monu ◽  
Paola Pesce ◽  
Stephen J Peterson ◽  
Komal Sodhi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Cardiac Function ◽  
Heme Oxygenase ◽  
Angiogenic Factors ◽  
Heme Oxygenase 1 ◽  
Artery Ligation ◽  
Capillary Formation ◽  
Beneficial Effects ◽  
Angiogenic Proteins

Rational: Angiogenesis is essential in order to increase blood circulation in infarcted tissue of MI (Myocardial infarction). Increased Heme-Oxygenase (HO)-1 gene expression increases angiogenic proteins, e.g. VEGF, bFGF, EGF, angiopoietin and adiponectin. Objective: To investigate whether increased levels of HO-1, after the occurrence of a MI, improves angiogenesis and capillary formation in ischemic myocardium, thereby improving cardiac function. METHODS: Experimental MI was induced by LAD (Left anterior descending artery) ligation. C57BL6 mice were divided into 4 groups: Sham; MI; 5 days after MI treated with the HO-1 inducer, cobalt protoporphyrinIX (CoPP); and, CoPP in the presence of the HO activity inhibitor, Stannous Mesoporphyrin (SnMP). HO-1 downstream signaling proteins were determined including VEGF, CD31 and adiponectin. Echocardiography was performed weekly for 4 weeks after surgery. Results: 5 days after MI, CoPP treatment significantly increased VEGF (p<0.05 vs.MI), CD31 (p<0.05 vs.MI), and adiponectin levels (p<0.05 vs.MI). These findings were associated with a significant increase in capillary formation and blood flow in CoPP-treated animals (p<0.05 vs.MI). Echocardiography showed that left ventricle dilatation, measured as end diastolic area (EDA), was significantly reduced in CoPP- treated animals compared to MI groups (EDA: MI: 0.216±0.02cm2; MI+CoPP: 0.172±0.03 cm2; (-13%) p<0.01). This was associated with a significant decrease in apoptosis and fibrosis (P<0.05). These beneficial effects were reversed by SnMP administration. Conclusion: HO-1 improved cardiac function and enhanced angiogenesis via the recruitment of pro-angiogenic factors.

Role of Heme Oxygenase-1 in the Regulation of Blood Pressure and Cardiac Function

2003 ◽  
Vol 228 (5) ◽  
pp. 447-453 ◽  
Author(s):  
Yen-Hsu Chen ◽  
Shaw-Fang Yet ◽  
Mark A. Perrella
Keyword(s):  
Blood Pressure ◽  
Cardiac Function ◽  
Reperfusion Injury ◽  
Heme Oxygenase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Heme Oxygenase 1 ◽  
Coronary Artery Ligation ◽  
Regulation Of Blood Pressure

Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of the properties of inducible HO (HO-1) and its products, we hypothesized that HO-1 would play an important role in the regulation of cardiovascular function. In this article, we will review the role of HO-1 in the regulation of blood pressure and cardiac function and highlight previous studies from our laboratory using gene deletion and gene overexpression transgenic approaches in mice. These studies will include the investigation of HO-1 in the setting of hypertension (renovascular), hypotension (endotoxemia), and ischemia/reperfusion injury (heart). In a chronic renovascular hypertension model, hypertension, cardiac hypertrophy, acute renal failure, and acute mortality induced by one kidney–one clip surgery were more severe in HO-1-null mice. In addition, HO-1-null mice with endotoxemia had earlier resolution of hypotension, yet the mortality and the incidence of end-organ damage were higher in the absence of HO-1. In contrast, mice with cardiac-specific overexpression of HO-1 had an improvement in cardiac function, smaller myocardial infarctions, and reduced inflammatory and oxidative damage after coronary artery ligation and reperfusion. Taken together, these studies suggest that an absence of HO-1 has detrimental consequences, whereas overexpression of HO-1 plays a protective role in hypoperfusion and ischemia/reperfusion injury.

Stimulation of haematopoiesis in murine model of myocardial infarction. Role of heme oxygenase 1

2016 ◽  
Vol 33 ◽  
pp. S77-S78
Author(s):  
Mateusz Tomczyk ◽  
Krzysztof Szade ◽  
Izabela Kraszewska ◽  
Karolina Bukowska-Strakova ◽  
Alicja Józkowicz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heme Oxygenase ◽  
Murine Model ◽  
Heme Oxygenase 1 ◽  
Stimulation Of

scholarly journals Targeting Heme Oxygenase-1 in Cardiovascular and Kidney Disease

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 181 ◽  
Author(s):  
Heather A. Drummond ◽  
Zachary L. Mitchell ◽  
Nader G. Abraham ◽  
David E. Stec
Keyword(s):  
Blood Pressure ◽  
Cardiovascular System ◽  
Heme Oxygenase ◽  
Critical Role ◽  
Organ Injury ◽  
Renal Diseases ◽  
Heme Oxygenase 1 ◽  
Benefit Patient ◽  
Regulation Of Blood Pressure

Heme oxygenase (HO) plays an important role in the cardiovascular system. It is involved in many physiological and pathophysiological processes in all organs of the cardiovascular system. From the regulation of blood pressure and blood flow to the adaptive response to end-organ injury, HO plays a critical role in the ability of the cardiovascular system to respond and adapt to changes in homeostasis. There have been great advances in our understanding of the role of HO in the regulation of blood pressure and target organ injury in the last decade. Results from these studies demonstrate that targeting of the HO system could provide novel therapeutic opportunities for the treatment of several cardiovascular and renal diseases. The goal of this review is to highlight the important role of HO in the regulation of cardiovascular and renal function and protection from disease and to highlight areas in which targeting of the HO system needs to be translated to help benefit patient populations.

Functional Expression of Human Heme Oxygenase-1 Gene in Renal Structure of Spontaneously Hypertensive Rats

2003 ◽  
Vol 228 (5) ◽  
pp. 454-458 ◽  
Author(s):  
Alvin I. Goodman ◽  
Shou Quan ◽  
Liming Yang ◽  
Arika Synghal ◽  
Nader G. Abraham
Keyword(s):  
Blood Pressure ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Rat Kidney ◽  
Functional Expression ◽  
Heme Oxygenase 1 ◽  
Thick Ascending Limb ◽  
Bile Pigments ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Heme oxygenase (HO), by catabolizing heme to bile pigments, regulates the levels and activity of cellular hemoprotein and HO activity. We examined the effect of delivery of the human HO-1 gene on cellular heme in renal tissue using a retroviral vector. We used a single intracardiac injection of the concentrated infectious viral particles in 5-day-old spontaneously hypertensive rats; 25 were transduced with empty vector and 25 were transduced with the human HO-1 gene. Functional expression of human and rat HO-1 was measured after 2 and 4 weeks. Reverse transcription polymerase chain reaction showed that human HO-1 mRNA was expressed as early as 2 weeks, with the highest levels in the kidney. Western blot analysis showed distribution of human HO-1 protein in rat kidney structures, predominantly in the thick ascending limb of the loop of Henle as well as in proximal tubules and preglomerular arterioles. These areas also demonstrated higher HO activity as measured by increased conversion of heme to bilirubin and carbon monoxide. Functional expression of the human HO-1 gene was associated with a decrease in blood pressure in 4- and 8-week-old spontaneously hypertensive rats. Compared with nontransduced rats, human HO-1 gene overexpression in transduced rats was associated with a 35% decrease in urinary 20-hydroxyeicosatetraenoic acid, a potent vasoconstrictor and an inhibitor of tubular Na+ transport, which may be related to the decrease in blood pressure.

Association of heme oxygenase-1 gene promoter polymorphism and blood pressure in an Iranian population

2014 ◽  
Vol 44 (9) ◽  
pp. 931-932 ◽  
Author(s):  
F. Haghdoost ◽  
S. H. Javanmard ◽  
K. Keyhanian ◽  
A. A. Samety ◽  
P. Loghmani ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heme Oxygenase ◽  
Gene Promoter ◽  
Promoter Polymorphism ◽  
Iranian Population ◽  
Heme Oxygenase 1 ◽  
Gene Promoter Polymorphism

Heme oxygenase-1 induction protects the heart and modulates cellular and extracellular remodelling after myocardial infarction in rats

2011 ◽  
Vol 236 (12) ◽  
pp. 1437-1448 ◽  
Author(s):  
Päivi Lakkisto ◽  
Juha-Matti Siren ◽  
Ville Kytö ◽  
Hanna Forsten ◽  
Mika Laine ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

Transfer of the Human Heme Oxygenase-1 Gene Decreases Blood Pressure and Promotes Growth in Spontaneously Hypertensive Rats

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 730-730
Author(s):  
Hatem E Sabaawy ◽  
Fan Zhang ◽  
Alberto Nasjletti ◽  
Michal Laniado-Schwartzman ◽  
Nader G Abraham
Keyword(s):  
Blood Pressure ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Body Weight Gain ◽  
Retroviral Vector ◽  
Left Ventricular ◽  
Intraluminal Pressure ◽  
Heme Oxygenase 1 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

P203 Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, free iron and carbon monoxide (CO). Both heme and CO have been implicated in the regulation of vascular tone. We report the successful cloning of the human HO-1 cDNA (HHO-1) into a LXSN retroviral vector (LSN-HHO-1). A single intra-left ventricular delivery of 1×10 10 pfu/ml of LSN-HHO-1 to 5-day-old spontaneously hypertensive rats (SHR; n = 32) resulted in extended expression of the human HO-1 (mRNA and protein) in several tissues, including the kidney, liver, spleen, lung, heart, brain and aorta. The expression of HHO-1 was associated with a 2-3 fold increase in HO activity in these tissues. Mean blood pressure (MBP) of SHR injected with LSN-HHO-1 was significantly lower than that of SHR injected with the control empty vector LXSN, by 4 weeks of age (144±4.6 mmHg vs 164.8±6.5 mmHg, n=32, * p <0.01). SHR treated with LSN-HHO-1 demonstrated a consistent reduction in MBP of ≈20 ± 4 mmHg when compared with the control LXSN injected SHR throughout the 20 weeks of the experiment. Administration of the HO inhibitor, stannic mesoporphyrin (Sn MP), to LSN-HHO-1-treated SHR resulted in a 15 to 18 mmHg rise of MBP, further suggesting that increased HO expression underlie, at least in part, the blood pressure lowering effect of LSN-HHO-1. Rats expressing HHO-1 showed significant reduction in the urinary excretion of the vasoconstrictor cytochrome P-450 arachidonate metabolite, 20-HETE. Moreover, gracilis muscle arterioles (≈ 55μm in diameter) isolated from HHO-1 transgenic SHR showed less contractile responses to increased intraluminal pressure than vessels isolated from LXSN-treated SHR; this effect was reversed by the addition of SnMP. Interestingly, HHO-1 transgenic rats showed significant proportionate increase in somatic growth, i.e., nose to tail length, fibula length and body weight gain. These studies demonstrate that delivery of the human HO-1 gene by a retroviral vector results in permanent expression of HHO-1, long-term reduction in blood pressure together with growth promoting activity in the SHR.

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