scholarly journals Endocardial Endothelial Dysfunction and Unknown Polymorphic Composite Accumulation in Heart Failure

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1465
Author(s):  
Hsuan-Fu Kuo ◽  
I-Fan Liu ◽  
Chia-Yang Li ◽  
Chien-Sung Tsai ◽  
Yung-Hsiang Chen ◽  
...  

The accumulation of unknown polymorphic composites in the endocardium damages the endocardial endothelium (EE). However, the composition and role of unknown polymorphic composites in heart failure (HF) progression remain unclear. Here, we aimed to explore composite deposition during endocardium damage and HF progression. Adult male Sprague–Dawley rats were divided into two HF groups—angiotensin II-induced HF and left anterior descending artery ligation-induced HF. Heart tissues from patients who had undergone coronary artery bypass graft surgery (non-HF) and those with dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) were collected. EE damage, polymorphic unknown composite accumulation, and elements in deposits were examined. HF progression reduced the expression of CD31 in the endocardium, impaired endocardial integrity, and exposed the myofibrils and mitochondria. The damaged endocardial surface showed the accumulation of unknown polymorphic composites. In the animal HF model, especially HF caused by myocardial infarction, the weight and atomic percentages of O, Na, and N in the deposited composites were significantly higher than those of the other groups. The deposited composites in the human HF heart section (DCM) had a significantly higher percentage of Na and S than the other groups, whereas the percentage of C and Na in the DCM and ICM groups was significantly higher than those of the control group. HF causes widespread EE dysfunction, and EndMT was accompanied by polymorphic composites of different shapes and elemental compositions, which further damage and deteriorate heart function.

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Jian Zhang ◽  
Junjie Liu ◽  
Sheng Gao ◽  
Weili Lin ◽  
Pengrong Gao ◽  
...  

Qishen granules (QSG) are a famous formula with cardioprotective properties to heart failure (HF). The aim of this study was to investigate the underlying mechanism of QSG on apoptosis and fibrosis in the treatment of HF. HF model was induced by left anterior descending artery ligation on Sprague-Dawley rats. Transcriptome analysis was used to investigate the regulatory pathways of QSG on HF. Interestingly, downregulated genes of QSG were significantly enriched in Hippo pathway which plays a crucial role in regulating cell apoptosis and proliferation. We found that QSG inhibited the expressions of proapoptotic key proteins P-53 and fibrosis-related proteins TGF-β1, SMAD3, and CTGF. Further, we conducted research on the key proteins in the Hippo pathway upstream of CTGF and P-53. The results showed that MST1, P-MST1, P-LATS1, and RASSF1A that exert proapoptotic function were downregulated after QSG intervention. Similarly, P-YAP and P-TAZ, mediating self-degradation and apoptosis, were both observably decreased after QSG administration. Taken together, QSG are shown to be likely to exert cardioprotective effects by inhibiting the progression of apoptosis and fibrosis through Hippo pathway.


2001 ◽  
Vol 281 (4) ◽  
pp. H1767-H1770 ◽  
Author(s):  
Julia H. Indik ◽  
Steven Goldman ◽  
Mohamed A. Gaballa

Congestive heart failure (HF) is characterized by inadequate nitric oxide (NO) production in the vasculature. Because NO is degraded by oxygen radicals, we hypothesized that NO is degraded faster in HF from inadequate peripheral arterial antioxidant reserves. HF was induced in male Sprague-Dawley rats by left coronary artery ligation. Vascular endothelial function was evaluated by measuring the NO-mediated vasorelaxation response to acetylcholine (ACh; 10−9–10−4M) in excised aortas. This was repeated with the free radical generator pyrogallol (20 μM) and again with pyrogallol and superoxide dismutase (SOD; 60 U/ml). Aortic and myocardial SOD activity was also determined. ACh-induced vasorelaxation was reduced in HF ( n = 9) compared with normal control rats ( n = 11; P < 0.001). Pyrogallol further reduced vasorelaxation in HF: 74 ± 11% at 10−4M ACh versus 58 ± 10% in normal control rats ( P < 0.004). There was a trend ( P = 0.06) toward reduced SOD activity in HF aortas. In conclusion, altered NO-dependent vasorelaxation in HF is in part due to excessive degradation of NO and is likely related to reduced vascular SOD activity.


2019 ◽  
Vol 11 (10) ◽  
pp. 71
Author(s):  
Anwar A. Al-Assaff ◽  
Hamed R. Takruri

The objective of this study was to determine the effect of selected Jordanian wild edible plant on lipid peroxidation and lipid profile in adult male Sprague Dawley rats fed high-fat diet. Fiftysix male, adult Sprague-Dawley rats at eight weeks of age, weighing about 200g were distributed into 7 experimental groups, 7 rats each . The groups included a negative control group that was fed a normal fat diet (NFD) and a possitve control group that was fed a high fat diet (HFD) (45% calories from fat). The six treatment groups were fed a HFD for the first 4 weeks of the experiment and a HFD with 9% of one of the selected dried plants for another 4 weeks. The treatment groups are sumac, thyme, clary, gundelia, garden rocket and wild mint. Blood samples were collected from the right heart ventricle. Serum malondialdehyde, lipid profile and fasting blood glucose were measured for rats. Results showed that the addition of different dried plant powders to the HFD did not significantly affect serum levels of TG, TC, HDL, LDL and fasting blood glucose. On the other hand, malondialdehyde (MDA) levels were significantly (p &lt; 0.05) higher in the HFD group (4.09&plusmn;0.45 mmol/ml) than those of other groups. MDA serum levels for the other groups were as follows: NFD (2.47&plusmn;0.05), sumac (2.45&plusmn;0.13), thyme (2.88&plusmn;0.07), clary (2.97&plusmn;0.16), garden rocket (2.96&plusmn;0.11), gundelia (2.92&plusmn;0.16) and wild mint (2.68&plusmn;0.09). These levels were not sinificantly different from each other. It is concluded that incorporating dried plant powders in rat diets had a significantly positive effect only on lipid peroxidation assay as indicated by serum MDA levels.


Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1073
Author(s):  
Cristina Pop ◽  
Maria-Georgia Ștefan ◽  
Dana-Maria Muntean ◽  
Laurențiu Stoicescu ◽  
Adrian Florin Gal ◽  
...  

Obesity induces hemodynamic and humoral changes that are associated with functional and structural cardiac remodeling, which ultimately result in the development of heart failure (HF) with preserved ejection fraction (HFpEF). In recent years, pharmacological studies in patients with HFpEF were mostly unsatisfactory. In these conditions, alternative new therapeutic approaches are necessary. The aim of our study was (1) to assess the effects of obesity on heart function in an experimental model and (2) to evaluate the efficacy of an alpha-lipoic acid (ALA) antioxidant treatment. Sprague-Dawley rats (7 weeks old) were either included in the control group (n = 6) or subjected to abdominal aortic banding (AAB) and divided into three subgroups, depending on their diet: standard (AAB + SD, n = 8), hypecaloric (AAB + HD, n = 8) and hypecaloric with discontinuous ALA treatment (AAB + HD + ALA, n = 9). Body weight (BW), glycemia, echocardiography parameters and plasma hydroperoxides were monitored throughout the study. After 36 weeks, plasma adiposity (leptin and adiponectin) and inflammation (IL-6 and TNF-alpha) markers, together with B-type natriuretic peptide and oxidative stress markers (end-products of lipid peroxidation and endogenous antioxidant systems) were assessed. Moreover, cardiac fiber diameters were measured. In our experiment, diet-induced obesity generated cardiometabolic disturbances, and in association with pressure-overload induced by AAB, it precipitated the onset of heart failure, cardiac hypertrophy and diastolic dysfunction, while producing a pro-oxidant and pro-inflammatory plasmatic status. In relationship with its antioxidant effects, the chronic ALA-discontinuous treatment prevented BW gain and decreased metabolic and cardiac perturbations, confirming its protective effects on the cardiovascular system.


1987 ◽  
Vol 57 (01) ◽  
pp. 55-58 ◽  
Author(s):  
J F Martin ◽  
T D Daniel ◽  
E A Trowbridge

SummaryPatients undergoing surgery for coronary artery bypass graft or heart valve replacement had their platelet count and mean volume measured pre-operatively, immediately post-operatively and serially for up to 48 days after the surgical procedure. The mean pre-operative platelet count of 1.95 ± 0.11 × 1011/1 (n = 26) fell significantly to 1.35 ± 0.09 × 1011/1 immediately post-operatively (p <0.001) (n = 22), without a significant alteration in the mean platelet volume. The average platelet count rose to a maximum of 5.07 ± 0.66 × 1011/1 between days 14 and 17 after surgery while the average mean platelet volume fell from preparative and post-operative values of 7.25 ± 0.14 and 7.20 ± 0.14 fl respectively to a minimum of 6.16 ± 0.16 fl by day 20. Seven patients were followed for 32 days or longer after the operation. By this time they had achieved steady state thrombopoiesis and their average platelet count was 2.44 ± 0.33 × 1011/1, significantly higher than the pre-operative value (p <0.05), while their average mean platelet volume was 6.63 ± 0.21 fl, significantly lower than before surgery (p <0.001). The pre-operative values for the platelet volume and counts of these patients were significantly different from a control group of 32 young males, while the chronic post-operative values were not. These long term changes in platelet volume and count may reflect changes in the thrombopoietic control system secondary to the corrective surgery.


Author(s):  
Xiangyu Liu ◽  
Xiong Xue ◽  
Junsheng Tian ◽  
Xuemei Qin ◽  
Shi Zhou ◽  
...  

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.


Vascular ◽  
2021 ◽  
pp. 170853812199985
Author(s):  
Yuanyuan Guo ◽  
Fan Zhu ◽  
Xiong Zhang ◽  
Guangmin Wu ◽  
Pinting Fu ◽  
...  

Objectives Vein graft adaptation (VGA) is a process that vein as a vascular graft conduits in arterial reconstructive surgery; VGA can lead to postoperative vein graft stenosis (VGS) and complications after coronary artery bypass graft and other peripheral artery bypass surgeries. VGA is characterized by vein graft loss the venous features without exhibiting arterial features; furthermore, the activation of ERK inhibited the maintenance of venous properties of the vein graft. We hypothesized that ERK inhibition can affect vein VGS through regulating the expression of EphB4. Methods Rat vein transplantation model was established using wild-type and EphB4+/− Sprague-Dawley rats. Hematoxylin-eosin, Masson, Verhoeff, actin staining, and immunohistochemistry were applied to observe the structure of the vein grafts. Vascular smooth muscle cells (VSMCs) were isolated from the vein and vein grafts. Western blotting was used to determine the expression of p-ERK1/2 and EphB4, and immunofluorescence was applied to detect the expression and location of EphB4. Cell wound scratch assay and CCK8 assay were used to determine the migration and proliferation of VSMCs. Real-time polymerase chain reaction was used to determine the mRNA expression of EphB4. Results Western blotting in vein sample and vein graft sample detected p-ERK1/2 and ERK1/2 expression in both EphB4+/+ and EphB4+/− rats. The expression of p-ERK was increased in vein graft compared to vein. Immunofluorescence in VSMCs form EphB4+/+ and EphB4+/− rats detected EphB4 expression in both cells, and the expression of EphB4 was increased in VSMCs form EphB4+/+ rats. SCH772984 reduces the proliferation and migration of VSMCs. Inhibition of ERK suppressed the increase of vein graft wall thickness, and the expression of collagen fibers, elastic fibers, and α-actin was decreased. Vein graft from EphB4+/− rats reduces the expression of EphB4, and SCH772984 suppressed the decrease of EphB4 in vivo. Vein graft from EphB4+/− rats increased the expression of EphB4, and SCH772984 suppressed the increase of EphB4 in vivo. Conclusions The inhibition of ERK1/2 suppressed the process of VGS by decreasing the proliferation of VSMCs. The ERK-inhibitor SCH772984 suppressed the level of VGS by extending the time of EphB4 expression during the process of VGA, thus maintaining the venousization of vein graft. The mechanism may be that the inhibitor SCH772984 suppresses the level of VGS by extending the time of EphB4 expression during the process of VGA. Therefore, our research provides a new target of VGS treatment by inhibiting the expression of ERK1/2 through the process of VGA.


2009 ◽  
Vol 29 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Amal A El-Bakary ◽  
Sahar A El-Dakrory ◽  
Sohayla M Attalla ◽  
Nawal A Hasanein ◽  
Hala A Malek

Methanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.


2021 ◽  
Vol 9 ◽  
pp. 232470962110261
Author(s):  
Tuong Vi Cassandra Do ◽  
Justin Cozza ◽  
Shyam Ganti ◽  
Jayaramakrishna Depa

Chylothorax is a pleural effusion of >110 mg/dL of triglycerides with a milky appearance with transudative being rare. In this article, we present a case of transudative chylothorax with concurrent chylous ascites that is secondary to congestive heart failure (CHF). A 70-year-old male with CHF with ejection fraction of 10%, coronary artery disease status post coronary artery bypass graft, sleep apnea, chronic kidney disease stage 3, and chronic obstructive pulmonary disease presented with worsening abdominal distention, shortness of breath, and increased lower extremities edema. He denied any cough or fever but had orthopnea and paroxysmal nocturnal dyspnea. He requires monthly paracentesis with drainage of 5 to 9 L each time. On physical examination, he had crackles bilaterally with no wheezes or jugular venous distension. His cardiac examination was unremarkable. He did have abdominal distension with dullness to percussion and a positive fluid wave. There was +2 bilateral pitting edema of lower extremities. He had a diagnostic paracentesis where 9.2 L of cloudy milky fluid was drained and therapeutic thoracentesis where 1.1 L of milky fluid was drained. Pleural fluid for triglycerides was 280. His peritoneal fluid had triglycerides of 671 confirming chylous ascites. CHF can lead to chylous ascites due to the increased lymph production in the abdomen, which flows to the thoracic duct. Due to the stiffness at the lymphatic junction, there is high pressure for less flow. The diaphragm plays a role allowing the chylous ascites to be absorb into the thorax.


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