scholarly journals Knockdown of Salusin-β Improves Cardiovascular Function in Myocardial Infarction-Induced Chronic Heart Failure Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Yu Xu ◽  
Yan Pan ◽  
Xingxing Wang ◽  
Aidong Chen ◽  
Xinyu Tang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Chronic Heart Failure ◽  
Endothelial Function ◽  
Cardiac Function ◽  
Biologically Active ◽  
Coronary Artery Ligation ◽  
Myocardial Remodeling

Salusin-β is a biologically active peptide with 20 amino acids that exerts several cardiovascular activity-regulating effects, such as regulating vascular endothelial function and the proliferation of vascular smooth muscle cells. However, the regulatory effects of salusin-β in myocardial infarction-induced chronic heart failure (CHF) are still unknown. The current study is aimed at investigating the effects of silencing salusin-β on endothelial function, cardiac function, vascular and myocardial remodeling, and its underlying signaling pathways in CHF rats induced by coronary artery ligation. CHF and sham-operated (Sham) rats were subjected to tail vein injection of adenoviral vectors encoding salusin-β shRNA or a control-shRNA. The coronary artery (CA), pulmonary artery (PA), and mesenteric artery (MA) were isolated from rats, and isometric tension measurements of arteries were performed. Compared with Sham rats, the plasma salusin-β, leptin and visfatin levels and the salusin-β protein expression levels of CA, PA, and MA were increased, while the acetylcholine- (ACh-) induced endothelium-dependent vascular relaxation of CA, PA, and MA was attenuated significantly in CHF rats and was improved significantly by salusin-β gene knockdown. Salusin-β knockdown also improved cardiac function and vascular and myocardial remodeling, increased endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) levels, and decreased NAD(P)H oxidase activity, NOX-2 and NOX-4 expression, and reactive oxygen species (ROS) levels in arteries in CHF rats. The effects of salusin-β knockdown in CHF rats were attenuated significantly by pretreatment with the NOS inhibitor L-NAME. These results indicate that silencing salusin-β contributes to the improvement of endothelial function, cardiac function, and cardiovascular remodeling in CHF by inhibiting NAD(P)H oxidase-ROS generation and activating eNOS-NO production.

Abstract 2419: Left Ventricle Function Preservation by a Novel Synthetic Hydrogel Injection in Myocardial Infarction Rabbit

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Xiaoyan Li ◽  
Xuejun Jliang ◽  
Tao Wang ◽  
Taol Lin ◽  
Congxin Huang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Left Ventricle ◽  
Ethylene Glycol ◽  
Control Group ◽  
Coronary Artery Ligation ◽  
Poly Ethylene Glycol ◽  
Infarcted Myocardium ◽  
Poly Ethylene

Myocardial infarction and the subsequent heart failure remain among the world’s prominent health challenges. Other studies have demonstrated that bio-derived materials improve cardiac function after implantation for angiogenic potential. In this study, we hypothesized that injection of biomaterials into infarcted myocardium can preserve left ventricle (LV) function through its prevention of paradoxical systolic bulging. Infarction was induced in rabbit myocardium by coronary artery ligation. In sham-operated rabbits (n = 5), a suture was tied loosely around the left anterior descending coronary artery without ligating it. 7 dayslater, 100μl α-cyclodextrin (CD) solution and 100μl poly (ethylene glycol)-b-polycaprolactone-(dodecanedioic acid)-polycaprolactone-poly (ethylene glycol)(MPEG-PCL-MPEG) solution (n = 7) was injected simultaneously through Duploject applicator into the infarcted myocardium. Solid hydrogel matrix formed by linear MPEG-PCL-MPEG polymer threading into the cavities of the α-cyclodextrin after mixing. Injection of phosphate buffered saline (PBS) served as controls (n = 7). 28 days after the treatments, histological analysis indicated that injection of hydrogel prevented scar expansion and wall thinning compared with group ( P < 0.05) without more microvessel density in infarcted myocardium ( P = 0.70).By echocardiography, LV ejection fraction was significantly greater in the hydrogel group (56.09 ± 8.42%) than the control group (37.26 ± 6.36%, P = 0.001). The LV end-diastolic and end-systolic diameters were 2.07 ± 0.33 cm and 1.74 ± 0.30cm in the control group, respectively. Smaller LV end-diastolic diameter (1.61 ± 0.26cm, P = 0.005) and smaller end-systolic diameter (1.17 ± 0.23cm, P = 0.001) were found in the hydrogel group. These results suggest that α-CD/MPEG-PCL-MPEG hydrogel injection could serve structural and mechanical support of an injured LV replacing some of the functions of the damaged ECM and thus prevented paradoxical motion serves, which may eventually lead to LV remodeling and dilation prevention. Our study should initiate further experimental and clinical studies exploring potential approaches to the treatment of postinfarction heart failure.

Effects of Amlodipine on Endothelial Function in Rats with Chronic Heart Failure After Experimental Myocardial Infarction

1997 ◽  
Vol 30 (5) ◽  
pp. 683-689 ◽  
Author(s):  
Rob J. M. de Vries ◽  
Rutger Anthonio ◽  
Dirk J. van Veldhuisen ◽  
Egbert Scholtens ◽  
Hendrik Buikema ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Endothelial Function ◽  
Experimental Myocardial Infarction

Atrial natriuretic peptide transcription, storage, and release in rats with myocardial infarction

1987 ◽  
Vol 253 (6) ◽  
pp. H1449-H1455 ◽  
Author(s):  
R. E. Mendez ◽  
J. M. Pfeffer ◽  
F. V. Ortola ◽  
K. D. Bloch ◽  
S. Anderson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Infarct Size ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Mrna Levels ◽  
Atrial Natriuretic

To study the role of atrial natriuretic peptide (ANP) in chronic heart failure, ANP synthesis, storage, and release were examined by measuring atrial ANP messenger ribonucleic acid (mRNA) levels and atrial and plasma ANP concentrations in rats with myocardial infarction produced by coronary artery ligation. Three groups were defined as the following: 1) controls, sham-operated, or operated, but noninfarcted; 2) moderate infarcts, involving 5-30% of the left ventricular circumference; and 3) large infarcts (greater than or equal to 30%). In addition, to determine a possible modulation by dietary Na intake on ANP levels in heart failure, plasma immunoreactive ANP (iANP) levels were measured in rats with and without infarcts given low, regular, or high Na intake for 2 wk, by which time all groups were in neutral balance. Plasma iANP levels varied directly with increasing infarct and atrial sizes, irrespective of Na intake. In contrast, atrial ANP concentration varied inversely with increasing infarct size. The ANP mRNA content index, a measure of total atrial ANP mRNA, was significantly increased in rats with large infarcts compared with control rats. These results indicate that in rats with myocardial infarction, the severity of left ventricular dysfunction, as inferred from infarct size, but not chronic Na intake, is the primary determinant of the extent of activation of the ANP system. Elevated circulating ANP levels are maintained through enhanced atrial synthesis and release. ANP may thus play an important role in the hemodynamic and renal adaptations to chronic heart failure.

Acute Effects of Vitamin C on Platelet Responsiveness to Nitric Oxide Donors and Endothelial Function in Patients with Chronic Heart Failure

2001 ◽  
Vol 37 (5) ◽  
pp. 564-570 ◽  
Author(s):  
Gethin R. Ellis ◽  
Richard A. Anderson ◽  
Yuliy Y. Chirkov ◽  
Jayne Morris-Thurgood ◽  
Simon K. Jackson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Vitamin C ◽  
Endothelial Function ◽  
Nitric Oxide Donors ◽  
Acute Effects

Significance of changes in TNF-α and IL-10 levels in the progression of heart failure subsequent to myocardial infarction

2006 ◽  
Vol 291 (1) ◽  
pp. H106-H113 ◽  
Author(s):  
K. Kaur ◽  
A. K. Sharma ◽  
P. K. Singal
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Cardiac Function ◽  
Interleukin 10 ◽  
Mrna Levels ◽  
Protein Ratio ◽  
Protein Levels ◽  
Tnf Α ◽  
Membrane Bound

We tested whether a decrease in the ratio of interleukin-10 (IL-10) to tumor necrosis factor-α (TNF-α) correlates with the decrease in cardiac function in heart failure. It has been suggested that TNF-α plays a role in the progression of heart failure, and the effect of TNF-α in many tissues is modulated by IL-10. Any relation of these two cytokines to heart failure has never been examined. Cardiac function was assessed by echocardiographic and hemodynamic techniques in coronary artery-ligated rats at 1, 4, 8, and 16 wk after myocardial infarction (MI). Membrane-bound and soluble fractions of TNF-α and IL-10 proteins, the ratio of TNF-α to IL-10, and TNF-α and IL-10 mRNA levels were analyzed. Losartan was used to modify cardiac function in rats 4 wk after MI to further validate the relation between the IL-10-to-TNF-α ratio and cardiac function. Cardiac function deteriorated with time in all coronary artery-ligated groups, with severe failure at 16 wk after MI. Membrane-bound and soluble TNF-α protein fractions were increased 1 and 4 wk after MI, whereas TNF -α mRNA was increased 4 and 8 wk after MI. Membrane-bound IL-10 protein and mRNA levels were decreased 4, 8, and 16 wk after MI. The decrease in the IL-10-to-TNF-α protein ratio in all coronary artery-ligated groups correlated with the depressed cardiac function. Losartan improved cardiac function, membrane-bound and soluble TNF-α and IL-10 protein levels, the ratio of IL-10 to TNF-α, and IL-10 mRNA. This study suggests that a decrease in IL-10 and IL-10-to-TNF-α ratio correlates with depressed cardiac function.

scholarly journals ERK1/2 MAPK signaling in hypothalamic paraventricular nucleus contributes to sympathetic excitation in rats with heart failure after myocardial infarction

2016 ◽  
Vol 310 (6) ◽  
pp. H732-H739 ◽  
Author(s):  
Yang Yu ◽  
Shun-Guang Wei ◽  
Zhi-Hua Zhang ◽  
Robert M. Weiss ◽  
Robert B. Felder
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Paraventricular Nucleus ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Mapk Signaling ◽  
Coronary Artery Ligation ◽  
Nerve Activity ◽  
Artery Ligation

Brain MAPK signaling pathways are activated in heart failure (HF) induced by myocardial infarction and contribute to augmented sympathetic nerve activity. We tested whether decreasing ERK1/2 (also known as p44/42 MAPK) signaling in the hypothalamic paraventricular nucleus (PVN), a forebrain source of presympathetic neurons, would reduce the upregulation of sympathoexcitatory mediators in the PVN and augmented sympathetic nerve activity in rats with HF. Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce HF, with left ventricular dysfunction confirmed by echocardiography. One week after coronary artery ligation or sham operation, small interfering (si)RNAs targeting ERK1/2 or a nontargeting control siRNA was microinjected bilaterally into the PVN. Experiments were conducted 5–7 days later. Confocal images revealed reduced phosphorylated ERK1/2 immunofluorescence in the PVN of HF rats treated with ERK1/2 siRNAs compared with HF rats treated with control siRNA. Western blot analysis confirmed significant reductions in both total and phosphorylated ERK1/2 in the PVN of HF rats treated with ERK1/2 siRNAs along with reduced expression of renin-angiotensin system components and inflammatory mediators. HF rats treated with ERK1/2 siRNAs also had reduced PVN neuronal excitation (fewer Fos-related antigen-like-immunoreactive neurons), lower plasma norepinephrine levels, and improved peripheral manifestations of HF compared with HF rats treated with control siRNAs. These results demonstrate that ERK1/2 signaling in the PVN plays a pivotal role in mediating sympathetic drive in HF induced by myocardial infarction and may be a novel target for therapeutic intervention.

scholarly journals Variability in coronary artery anatomy affects consistency of cardiac damage after myocardial infarction in mice

2017 ◽  
Vol 313 (2) ◽  
pp. H275-H282 ◽  
Author(s):  
Jiqiu Chen ◽  
Delaine K. Ceholski ◽  
Lifan Liang ◽  
Kenneth Fish ◽  
Roger J. Hajjar
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Left Coronary Artery ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Fluorescent Imaging ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Functional Parameters

Low reliability and reproducibility in heart failure models are well established. The purpose of the present study is to explore factors that affect model consistency of myocardial infarction (MI) in mice. MI was induced by left coronary artery (LCA) ligation. The coronary artery was casted with resin and visualized with fluorescent imaging ex vivo. LCA characteristics and MI size were analyzed individually in each animal, and MI size was correlated with left ventricular (LV) function by echocardiography. Coronary anatomy varies widely in mice, posing challenges for surgical ligation and resulting in inconsistent MI size postligation. The length of coronary arterial trunk, level of bifurcation, number of branches, and territory supplied by these branches are unique in each animal. When the main LCA trunk is ligated, this results in a large MI, but when a single branch is ligated, MI size is variable due to differing levels of LCA ligation and area supplied by the branches. During the ligation procedure, nearly 40% of LCAs are not grossly visible to the surgeon. In these situations, the surgeon blindly sutures a wider and deeper area of tissue in an attempt to catch the LCA. Paradoxically, these situations have greater odds of resulting in smaller MIs. In conclusion, variation in MI size and LV function after LCA ligation in mice is difficult to avoid. Anatomic diversity of the LCA in mice leads to inconsistency in MI size and functional parameters, and this is independent of potential technical modifications made by the operator. NEW & NOTEWORTHY In the present study, we demonstrate that left coronary artery diversity in mice is one of the primary causes of variable myocardial infarction size and cardiac functional parameters in the left coronary artery ligation model. Recognition of anatomic diversity is essential to improve reliability and reproducibility in heart failure research.

Na+/H+ exchange inhibition reduces hypertrophy and heart failure after myocardial infarction in rats

2001 ◽  
Vol 280 (2) ◽  
pp. H738-H745 ◽  
Author(s):  
Keiji Kusumoto ◽  
James V. Haist ◽  
Morris Karmazyn
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Hydrogen Exchange ◽  
Diastolic Pressure ◽  
Control Diet ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Large Infarct

We investigated the effect of sodium/hydrogen exchange inhibition (NHE-1) on hypertrophy and heart failure after coronary artery ligation (CAL) in the rat. Animals were subjected to occlusion (or sham) of the left main coronary artery and immediately administered a control diet or one consisting of the NHE-1 inhibitor cariporide for 13–15 wk. Hearts were separated by small [≤30% of left ventricle (LV)] and large (>30% of LV) infarcts. CAL depressed change in left ventricular increase in pressure over time (LV +dP/d t) in small and large infarct groups by 18.8% ( P < 0.05) and 34% ( P < 0.01), respectively, whereas comparative values for the cariporide groups were 8.7% (not significant) and 23.1% ( P < 0.01), respectively. LV end-diastolic pressure was increased by 1,225% in the control large infarct group but was significantly reduced to 447% with cariporide. Cariporide also significantly reduced the degree of LV dilation in animals with large infarcts. Hypertrophy, defined by tissue weights and cell size, was reduced by cariporide, and shortening of surviving myocytes was preserved. Infarct sizes were unaffected by cariporide, and the drug had no influence on either blood pressure or the depressed inotropic response of infarcted hearts to dobutamine. These results suggest an important role for NHE-1 in the progression of heart failure after myocardial infarction.

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