scholarly journals Clinical Evidence for Q10 Coenzyme Supplementation in Heart Failure: From Energetics to Functional Improvement

2020 ◽  
Vol 9 (5) ◽  
pp. 1266 ◽  
Author(s):  
Anna Di Lorenzo ◽  
Gabriella Iannuzzo ◽  
Alessandro Parlato ◽  
Gianluigi Cuomo ◽  
Crescenzo Testa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Oxidative Phosphorylation ◽  
Functional Improvement ◽  
Reduced Form ◽  
Clinical Effects ◽  
Safety Issues ◽  
Coq10 Deficiency ◽  
Hemodynamic Profile ◽  
Membrane Stabilizer ◽  
Coq10 Supplementation

Oxidative stress and mitochondrial dysfunction are hallmarks of heart failure (HF). Coenzyme Q10 (CoQ10) is a vitamin-like organic compound widely expressed in humans as ubiquinol (reduced form) and ubiquinone (oxidized form). CoQ10 plays a key role in electron transport in oxidative phosphorylation of mitochondria. CoQ10 acts as a potent antioxidant, membrane stabilizer and cofactor in the production of adenosine triphosphate by oxidative phosphorylation, inhibiting the oxidation of proteins and DNA. Patients with HF showed CoQ10 deficiency; therefore, a number of clinical trials investigating the effects of CoQ10 supplementation in HF have been conducted. CoQ10 supplementation may confer potential prognostic advantages in HF patients with no adverse hemodynamic profile or safety issues. The latest evidence on the clinical effects of CoQ10 supplementation in HF was reviewed.

scholarly journals One-year outcome of coenzyme Q10 supplementation in ADCK3 ataxia (ARCA2)

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Tommaso Schirinzi ◽  
Martina Favetta ◽  
Alberto Romano ◽  
Andrea Sancesario ◽  
Susanna Summa ◽  
...  
Keyword(s):  
Coenzyme Q10 ◽  
Rating Scales ◽  
Clinical Effects ◽  
Short Treatment ◽  
Oral Supplementation ◽  
Coq10 Deficiency ◽  
Pathophysiological Role ◽  
Coq10 Supplementation ◽  
One Year ◽  
Biallelic Mutations

Abstract Background The recessive ataxia ARCA2 is a rare disorder characterized by Coenzyme Q10 (CoQ10) deficiency due to biallelic mutations in ADCK3 gene. Despite the pathophysiological role, available data are not univocal on clinical efficacy of CoQ10 supplementation in ARCA2. Here we described the long-term motor outcome of 4 untreated ARCA2 patients prospectively followed-up for one year after starting CoQ10 oral supplementation (15 mg/kg/day). Methods Clinical rating scales (SARA; 9 holes peg test; 6 min walking test; Timed 25-Foot Walk) and videoelectronic gait analysis were performed at baseline and every 6 months (T0, T1, T2) to evaluate the motor performances. Since two patients discontinued the treatment at the 7th month, we could provide comparative analysis between longer and shorter supplementation. Results At T2, the gait speed (Timed 25-Foot Walk test) significantly differed between patients with long and short treatment; overall, the clinical condition tended to be better in patients continuing CoQ10. Conclusions Although preliminarily, this observation suggests that only prolonged and continuous CoQ10 supplementation may induce mild clinical effects on general motor features of ARCA2. Dedicated trials are now necessary to extend and validate such observation.

scholarly journals Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects

2021 ◽  
Vol 22 (11) ◽  
pp. 5863
Author(s):  
Giuseppe Palmiero ◽  
Arturo Cesaro ◽  
Erica Vetrano ◽  
Pia Clara Pafundi ◽  
Raffaele Galiero ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucose Transporter ◽  
The Elderly ◽  
Intracellular Sodium ◽  
Clinical Effects ◽  
Glucose Lowering ◽  
Beneficial Effects ◽  
Glucose Transporter 2 ◽  
Function Impairment

Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients’ exposure to gliflozins’ treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events.

Short-term and long-term hemodynamic and clinical effects of metoprolol alone and combined with amlodipine in patients with chronic heart failure

1999 ◽  
Vol 138 (2) ◽  
pp. 261-268 ◽  
Author(s):  
Marrick L. Kukin ◽  
Ronald S. Freudenberger ◽  
Michael M. Mannino ◽  
Jill Kalman ◽  
Marilyn Steinmetz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Clinical Effects ◽  
Short Term

Abstract P233: Diabetic Cardiomyopathy is Reversed by Increased Mitochondrial Bioenergetics Due to PGC-1α Activation by EET Treatment of Obese Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jian Cao ◽  
John A McClung ◽  
Shailendra P Singh ◽  
Lars Bellner ◽  
Maayan Waldman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Systolic Function ◽  
Control Group ◽  
Protein Markers ◽  
Obesity And Diabetes

Introduction: Obesity and diabetes are associated with progressive cardiac fibrosis that, sequentially, results in diastolic dysfunction, reduced contractility, and ultimately heart failure. Contributing factors include hyperglycemia, insulin resistance, mitochondrial dysfunction, and a reduction in AMPK signaling. PGC-1α activates mitochondrial biogenesis and oxidative phosphorylation and is decreased in patients with diabetes mellitus (DM). We hypothesize that an epoxyeicosatrienoic acids (EETs) agonist (EET-A) will increase PGC-1α levels in a db mouse model of DM attenuate cardiomyopathy, and prevent heart failure. Methods: Db mice (4-wks), were allowed to acclimatize for 16-wks and were then divided into 3 treatment groups for an additional 16 wks: A) control, B) EET-A 1.5mg/100g BW 2 weeks and C) EET-A-Ln-PGC-1α shRNA. Ln-PGC-1α shRNA suppressed PGC-1α protein in heart tissue by 40-50%. Oxygen consumption (VO 2 ), and blood glucose was determined. Heart tissues were harvested to measure PGC-1α, HO-1, pAMPK, PGC-1α, echocardiographic fractional shortening, mitochondrial oxidative phosphorylation (OXPHOS) and mitofusion protein markers. Results: All mice developed heart failure by the end of 16 weeks and were characterized by a decrease in myocardial contractility, an increase in insulin resistance and blood pressure, decreased VO 2 , the appearance of mitochondria dysfunction and a decrease in AMPK and downstream PGC-1α signaling. Mice treated with EET-A demonstrated an increase in PGC-1α levels, improved mitochondrial function and oxidative phosphorylation (p<0.01 vs control), increased NO bioavailability (p<0.05 vs control), and normalization of glucose metabolism, insulin levels, VO 2 and LV systolic function (p<0.05 vs control). All of these findings were suppressed by PGC-1α inhibition which was accompanied by the onset of even more severe LV dysfunction than in the control group. Conclusion: Increased EET levels result in activation of PGC-1α-HO-1 which reverses diabetes induced insulin resistance, mitochondrial dysfunction, and cardiomyopathy. EET may have potential as a powerful agent for therapeutic application in the treatment of diabetic cardiomyopathy.

Abstract 131: C-kit+ Cells Generated From Failed Heart Do Not Improve Failed Heart Function

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Liudmila Zakharova ◽  
Hikmet Nural ◽  
James R Nimlos ◽  
Snjezana Popovic ◽  
Lorraine Feehery ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricle ◽  
Diastolic Pressure ◽  
Heart Function ◽  
Smooth Muscle Actin ◽  
Functional Improvement ◽  
Gene Expressions ◽  
Coronary Vein ◽  
Mesenchymal Transition

A pilot clinical study using autologous c-Kit+ cells showed improvement in cardiac functions in congestive heart failure (CHF), however, it is unclear if c-Kit+ cells isolated from CHF hearts are equally as potent as cells from controls. To test the potency of CHF c-Kit+ cells, myocardial infarction (MI) was created by permanent ligation of the left anterior descending coronary artery. Six weeks after MI, animals with left ventricle end-diastolic pressure (LVEDP) ≥20 mmHg and scar size ≥30% of left ventricle (LV) were designated as CHF rats. We found that CHF atrial explants generated less c-Kit+ cells compared to shams (15.7% vs. 11% sham vs. CHF). CHF c-Kit+ cells exhibited elevated levels of epicardial to mesenchymal transition markers, including Snail (2.5 fold) and Pai1 (3 fold), while the expression level of epithelial marker, E-cadherin was 3 fold lower in CHF c-Kit+ cells. Moreover, CHF c-Kit+ cells exhibited reduced gene expressions of pluripotency markers; 2.1 fold decrease in Nanog and 4.5 fold decrease in Sox 2 compared to sham cells. To evaluate the potency of the c-Kit+ cells, 1 x 10 6 cells isolated from CHFs or shams were delivered to 3 weeks post-MI CHF hearts. Cells were pre-labeled with GFP to enable their tracing in vivo and delivered to the infarcted myocardium via left coronary vein by a retrograde coronary sinus cell infusion (RCI). RCI delivery resulted in a cell distribution of LV (30%), right atrium (30%) and right ventricle (20%), while only 10% of cells were found in a left atrium. Three weeks after cells delivery, rats transplanted with sham c-Kit+ cells showed improved LVEDP (29.4 ± 6 vs. 11.7 ± 3.5 mmHg, CHF vs. CHF+ sham c-Kit+ cells) and a rise in peak rate of pressure (dPdt max) (3988 ± 520 vs. 5333 ± 597 mmHg/s). In contrast, no functional improvement was detected in rats transplanted with CHF c-Kit+ cells. Histological analysis demonstrated that transplanted c-Kit+/GFP+ cells were mostly incorporated into blood vessels and co-localized with endothelial marker vWf, and α-smooth muscle actin. Our results showed that left coronary vein is an efficient route for c-Kit+ cell delivery and that c-Kit+ cells isolated from CHF rats are less potent when transplanted in chronic heart failure rat model compared to those isolated from control.

Abstract 13320: Direct Cardiac Actions of Empagliflozin Improve Mitochondrial Oxidative Phosphorylation and Attenuate Pressure-overload Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Xuan Li ◽  
Jussara M do Carmo ◽  
Zhen Wang ◽  
Alexandre A da Sivla ◽  
Alan J Mouton ◽  
...  
Keyword(s):  
Heart Failure ◽  
Molecular Docking ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Biogenesis ◽  
Glucose Transporters ◽  
Left Ventricular ◽  
Mitochondrial Morphology ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Docking Analysis ◽  
Molecular Docking Analysis

Introduction: The underlying mechanisms by which empagliflozin (EMPA) and other sodium glucose co-transporter 2 (SGLT2) inhibitors attenuate heart failure (HF) are still poorly understood. However, this protection does not appear to be fully explained by their antihyperglycemic or diuretic effects. Hypothesis: EMPA attenuates HF by direct effects on the heart to improve its metabolism and function. Methods: C57BL/6J mice (4-6 months) were subjected to transverse aortic constriction (TAC) or sham surgeries. Two weeks after TAC, EMPA (10 mg/kg/day) or vehicle was administered daily for 4 additional weeks. Cardiac function was assessed by echocardiography and cardiac substrate metabolism measured in isolated perfused hearts. Transmission electron microscopy was used to evaluate mitochondrial morphology and molecular docking analysis to predict potential cardiac targets of EMPA. Results: EMPA increased survival and attenuated adverse left ventricle remodeling and cardiac fibrosis after TAC. EMPA also attenuated left ventricular systolic dysfunction (ejection fraction 51.6 vs. 40.2% p<0.05; fraction shortening 28.8 vs 18.4% p<0.05). EMPA rescued impaired glucose and fatty acid oxidation in failing hearts, while reducing glycolysis. Molecular docking analysis and isolated perfused heart experiments indicated that EMPA can directly bind glucose transporters in the heart to reduce glycolysis, and enhance AMP-activated protein kinase. EMPA treatment enhanced mitochondrial biogenesis, restored mitochondria cristae integrity, increased expression of endogenous antioxidants, and reduced cellular apoptosis caused by leakage of cytochrome C from mitochondria into the cytosol. These beneficial cardiac effects of EMPA occurred despite no alterations in fasting blood glucose, body weight, or daily urine volume. Conclusions. Our study demonstrated that EMPA may directly bind glucose transporters and reduce excessive glycolysis in failing hearts. EMPA enhanced mitochondrial biogenesis, improved mitochondrial oxidative phosphorylation, and reduced mitochondria-mediated apoptosis, thereby attenuating cardiac dysfunction and progression of HF.

scholarly journals Tolvaptan in reversing worsening acute heart failure: A systematic review and meta-analysis

2019 ◽  
Vol 47 (11) ◽  
pp. 5414-5425
Author(s):  
Lili Wang ◽  
Qianhui Zhang ◽  
Meixia Liu ◽  
Shuxia Chen ◽  
Shuang Han ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Clinical Outcomes ◽  
Acute Heart Failure ◽  
Serum Sodium ◽  
Meta Analysis ◽  
Credible Interval ◽  
Current Evidence ◽  
Clinical Effects ◽  
Body Weight Reduction

Objective In this meta-analysis, we aimed to compare efficacy and clinical outcomes of tolvaptan in treating acute heart failure (AHF). Methods Using MEDLINE, we searched relevant clinical studies using tolvaptan that investigated clinical effects in treating AHF. We performed meta-analysis for potentially extractable clinical outcomes such as body weight reduction, change in serum sodium levels, and clinical or safety events including worsening heart failure, worsening renal function (WRF), all-cause mortality, rehospitalization, and dyspnea improvement. Results The results showed that tolvaptan significantly reduced body weight (mean change: −1.28 kg, 95% credible interval (CI): −1.58–0.98), increased serum sodium levels (mean change: 3.48 mmol/L; 95% Cl: 3.22–3.74), and improved dyspnea function (odds ratio (OR): 1.43; 95% CI: 1.26–1.62) versus conventional therapy. The event risk of WRF was also significantly reduced (OR: 0.35; 95% CI: 0.15–0.80). Low, intermediate, and high tolvaptan doses did not reduce mortality and rehospitalization risks. No significant publication bias was observed regarding effects on mortality and rehospitalization. Conclusion Current evidence indicates that using tolvaptan as add-on therapy can decrease body weight, increase sodium levels, improve dyspnea function, and reverse WRF, which may circumvent loop diuretics overdose and improve outcomes in patients with AHF.

Sign in / Sign up

Export Citation Format

Share Document