scholarly journals A Nano-Pharmaceutical Formula of Quercetin Protects from Cardiovascular Complications Associated with Metabolic Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Osama A. A. Ahmed ◽  
Noura A. Hassan ◽  
Ahmad S. Azhar ◽  
Mahmoud M. El-Mas ◽  
Hany M. El-Bassossy
Keyword(s):  
Metabolic Syndrome ◽  
Polyethylene Glycol ◽  
Left Ventricular Pressure ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Cardiac Damage ◽  
Pumpkin Seed ◽  
Cardiac Tissues ◽  
Standard Preparation ◽  
Dicrotic Notch

Metabolic syndrome (MetS) is closely associated with the development of cardiovascular diseases. We recently developed a nano-preparation of the flavonoid quercetin (QU) in a self-nanoemulsifying drug delivery system (SNEDDS). The latter comprised a mixture composed of pumpkin seed oil, D-α-Tocopherol polyethylene glycol 1,000 succinate and polyethylene glycol. The QU SNEDDS preparations exhibited a considerably higher bioavailability compared with the standard quercetin suspension. Here, we investigated whether the quercetin loaded SNEDDS could offer better protection compared with the standard formulation against cardiovascular complications of MetS in rats. MetS was induced by high fructose, high salt and high fat diet for 12 weeks while the nano-preparation or the standard suspension of quercetin was orally administered for the last 6 weeks. Compared to little effect for the standard quercetin suspension (MQ), the treatment of MetS rats with the quercetin loaded SNEDDS (MNQ) virtually abolished the depressant effect of MetS on contractility index (control, 114 ± 4; MetS, 92 ± 3; MQ, 100 ± 2; MNQ, 114 ± 6 1/s) and rate of rise in left ventricular pressure (dP/dtmax) (control, 8,171 ± 274; MetS, 6,664 ± 135; MQ, 6,776 ± 108; MNQ, 7,498 ± 303 mmHg/s). Likewise, the prolongation by MetS of electrocardiographic markers of arrhythmogenesis (QTc, JT, and Tpeak-to-Tend intervals) and concomitant rises in dicrotic notch pressure were preferentially reversed by quercetin nano-preparation. On the other hand, the rises in the isovolumic relaxation constant (Tau, denotes diastolic dysfunction), blood pressure, pulse pressure, and difference between systolic and dicrotic pressure (SDP difference) were equally improved by the two preparations of quercetin. Additionally, no differences were noted in the ability of the two quercetin preparations in abrogating the elevated oxidative (MDA) and inflammatory (TNFα) markers in cardiac tissues of MetS rats. Histopathological, microscopical signs of necrosis, inflammatory cell infiltration, and vascular congestion in MetS hearts were more markedly inhibited by the nano-preparation, compared with the standard preparation of quercetin. In conclusion, the quercetin loaded SNEDDS is evidently more advantageous than the standard preparation of the drug in alleviating functional and histopathological manifestations of cardiac damage incited by MetS.

scholarly journals Renovascular hypertension induces myocardial mitochondrial damage, contributing to cardiac injury and dysfunction in pigs with metabolic syndrome

2020 ◽  
Author(s):  
Arash Aghajani Nargesi ◽  
Mohamed C Farah ◽  
Xiang-Yang Zhu ◽  
Lei Zhang ◽  
Hui Tang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Renovascular Hypertension ◽  
Cardiac Fibrosis ◽  
Cardiac Injury ◽  
Left Ventricular ◽  
Mitochondrial Damage ◽  
Mitochondrial Morphology ◽  
H2o2 Production ◽  
Cardiac Damage ◽  
Cardiovascular Morbidity And Mortality

Abstract Background Subjects with renovascular hypertension (RVH) often manifest with metabolic syndrome (MetS) as well. Coexisting MetS and hypertension increases cardiovascular morbidity and mortality, but the mechanisms underlying cardiac injury remain unknown. We hypothesized that superimposition of MetS induces myocardial mitochondrial damage, leading to cardiac injury and dysfunction in swine RVH. Methods Pigs were studied after 16 weeks of diet-induced MetS with or without RVH (unilateral renal artery stenosis), and Lean controls (n=6 each). Systolic and diastolic cardiac function were assessed by multi-detector CT, and cardiac mitochondrial morphology (transmission electron microscopy) and myocardial function in tissue and isolated mitochondria. Results Body weight was similarly higher in MetS groups vs. Lean. RVH groups achieved significant stenosis and developed hypertension. Mitochondrial matrix density and ATP production were lower and H2O2 production higher in RVH groups versus Lean and MetS. Lean+RVH (but not MetS+RVH) activated mitophagy, which was associated with decreased myocardial expression of mitophagy-related microRNAs. MetS groups exhibited higher numbers of inter-mitochondrial junctions (IMJs), which could have prevented membrane depolarization/activation of mitophagy in MetS+RVH. Cardiac fibrosis, hypertrophy (increased left ventricular muscle mass), and diastolic function (decreased E/A ratio) were greater in MetS+RVH versus Lean+RVH. Conclusions Superimposition of MetS on swine RVH induces myocardial mitochondrial damage and dysfunction. MetS+RVH failed to activate mitophagy, resulting in greater cardiac remodeling, fibrosis, and diastolic dysfunction. Mitochondrial injury and impaired mitophagy may constitute important mechanisms and potential therapeutic targets to ameliorate cardiac damage and dysfunction in patients with coexisting MetS and RVH.

Abstract 300: Alda-1 Attenuates Acute Ischemia-reperfusion Mediated Cardiac Damage in Aldehyde Dehydrogenase 2 Mutant Diabetic Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Guodong Pan
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Acute Ischemia ◽  
Protective Effects ◽  
Diabetic Mice ◽  
Aldehyde Dehydrogenase 2 ◽  
Cardiac Damage ◽  
Western Blots

Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme in heart, can remove 4-hydroxy-2-nonenal (4-HNE), a toxic by-products of oxidative stress induced by diabetes and ischemia-reperfusion (I/R) injury. A common inactivating mutation of ALDH2 (termed ALDH2*2) was found in 8% of the world’s population, which causes lower ALDH2 activity in mutation carriers. We hypothesized that Alda-1, the only known activator of both ALDH2 and ALDH2*2 mutation, is able to protect heart from I/R injury in diabetic mice with/without ALDH2*2 mutation. Adult male ALDH2*2 mutant and C57B6 wild-type (WT) mice at 3-4 months of age were made hyperglycemic with streptozotocin injection (150 mg/kg. i.p.). Three weeks after injection, Alzet osmotic pumps were implanted subcutaneously to deliver Alda-1 (10 mg/kg) or vehicle. Mice were sacrificed after one day of pump implantation. Hearts were isolated and subjected to 30-minute ischemic followed by 90-minute reperfusion in a Langendorff apparatus. The basal myocardial ALDH2 activity in diabetic ALDH2*2 mutant was significantly lower than in diabetic WT mice (0.50±0.23 vs 0.83±0.08 mmol/min/μg, -39.8%, p<0.05). Alda-1 significantly increased myocardial ALDH2 activity in both ALDH2*2 (1.17±0.38 mmol/min/μg, +134.0%, p<0.05) and WT (1.46±0.40 mmol/min/μg, +75.9%, p<0.05) diabetic mice. Compared with vehicle, Alda-1 significantly improved left ventricular pressure (LVP), and decreased infarcted areas (IA) both in ALDH2*2 (LVP: 4.30±2.03 vs 15.77±8.99 mmHg, +266.7%, p<0.05; IA: 75.17%±9.49 vs 40.46%±7.20, -46.2%, p<0.05) and WT (LVP: 14.22±7.92 vs 21.96±4.32 mmHg, +54.4%, p<0.05; IA: 42.44%±8.60 vs 28.61%±8.55, -32.6%, p<0.05) subjected to I/R injury. Western-blots showed that Alda-1 decreased levels of 4-HNE protein adducts, and increased levels of mitochondrial complex V in both ALDH2*2 and WT mice. Our data suggest that one-day Alda-1 treatment can confer cardio-protective effects against I/R injury in ALDH2*2 diabetic mice possibly accelerating the detoxification of toxic 4-HNE and thereby protecting mitochondria.

Coronary artery ligation and reperfusion in rabbits made diabetic with alloxan

1987 ◽  
Vol 112 (1) ◽  
pp. 43-49 ◽  
Author(s):  
S. Bhimji ◽  
D. V. Godin ◽  
J. H. McNeill
Keyword(s):  
Coronary Artery ◽  
Left Ventricular Pressure ◽  
Clinical Situation ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Coronary Artery Ligation ◽  
Mitochondrial Atpase ◽  
Artery Ligation ◽  
Functional Changes

ABSTRACT The biochemical and functional changes associated with ligation (40 min) of the left circumflex coronary artery and subsequent reperfusion (60 min) in the rabbit made diabetic with alloxan were studied and compared with those of control animals. Measurement of haemodynamic parameters revealed that both left ventricular pressure and mean arterial pressure were significantly (P < 0·05) decreased after ligation and reperfusion in the diabetic animals compared with controls. Analysis of subcellular organelle enzyme markers from the ischaemic tissue revealed that sarcolemmal Na+,K+-ATPase, mitochondrial ATPase and sarcoplasmic reticulum ATPase activities were decreased after ligation to the same extent in the diabetic and control animals. However, upon reperfusion, the recovery of mitochondrial ATPase activity was significantly (P < 0·05) less in the diabetic animals than in the controls. Ion measurements revealed a significant (P < 0·05) depletion of Mg in diabetic hearts before ligation, and this was augmented during reperfusion. In contrast, a significantly (P < 0·05) higher calcium accumulation was observed upon reperfusion in the hearts of diabetic animals. Similarly, both tissue ATP levels and the ability of the mitochondria to generate ATP were depressed to a greater degree in the diabetic animals. Our results indicate, therefore, a greater susceptibility of the diabetic myocardium to ischaemic/reperfusion injury which in the clinical situation would exacerbate the problems associated with atherosclerosis and possibly contribute to the high mortality from cardiovascular complications in diabetic patients. J. Endocr. (1987) 112, 43–49

scholarly journals Cardiac Hypertrophy and Fibrosis in the Metabolic Syndrome: A Role for Aldosterone and the Mineralocorticoid Receptor

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Eric E. Essick ◽  
Flora Sam
Keyword(s):  
Metabolic Syndrome ◽  
Cardiac Hypertrophy ◽  
Cross Talk ◽  
Mineralocorticoid Receptor ◽  
Ventricular Hypertrophy ◽  
Cardiac Fibrosis ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
The Metabolic Syndrome ◽  
Increased Risk

Obesity and hypertension, major risk factors for the metabolic syndrome, render individuals susceptible to an increased risk of cardiovascular complications, such as adverse cardiac remodeling and heart failure. There has been much investigation into the role that an increase in the renin-angiotensin-aldosterone system (RAAS) plays in the pathogenesis of metabolic syndrome and in particular, how aldosterone mediates left ventricular hypertrophy and increased cardiac fibrosis via its interaction with the mineralocorticoid receptor (MR). Here, we review the pertinent findings that link obesity with elevated aldosterone and the development of cardiac hypertrophy and fibrosis associated with the metabolic syndrome. These studies illustrate a complex cross-talk between adipose tissue, the heart, and the adrenal cortex. Furthermore, we discuss findings from our laboratory that suggest that cardiac hypertrophy and fibrosis in the metabolic syndrome may involve cross-talk between aldosterone and adipokines (such as adiponectin).

scholarly journals Positive effects of renal denervation on left ventricular hypertrophy and subendocardial damage

2019 ◽  
Vol 25 (1) ◽  
pp. 46-59 ◽  
Author(s):  
E. S. Sitkova ◽  
V. F. Mordovin ◽  
T. M. Ripp ◽  
S. E. Pekarskii ◽  
T. R. Ryabova ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Renal Denervation ◽  
Ventricular Hypertrophy ◽  
Myocardial Damage ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Cardiac Damage ◽  
Positive Effects ◽  
One Year ◽  
Design And Methods

Background. The high prevalence of cardiac damage in resistant hypertensive patients signifcantly increases the risk of cardiovascular complications. Despite the antihypertensive effcacy of renal denervation (RDN), the cardioprotective effect has not been suffciently studied.Objective. To study the changes in left ventricular mass (LVM) and volume of myocardial damage after the RDN and to detect a possible connection of the studied parameters with blood pressure (BP) reduction after RDN.Design and methods. RDN was applied to 84 patients with resistant hypertension. Initially, at 6 and 12 months after treatment, patients underwent the measurements of the “offce” BP, 24-h BP, echocardiography and cardiac contrast-enhanced magnet-resistance tomography.Results. At baseline, “offce” BP averaged 175,3 ± 22,1 / 100,4 ± 16,1 mmHg and the prevalence of left ventricular hypertrophy (LVH) was 84,5 %. “Offce” BP reduced signifcantly at 6 month by –27,5 (–74,0; 12,0) / –14,2 (–39,4; 10,3) mmHg (p < 0,001), at 12 month by –31,6 (–78,7; 8,3) / –15,5 (–43,3; 10,2) mmHg (p < 0,001). 24-h BP reduced signifcantly at 6 month by –13,0 (–45,2; 17,6) / –6 (–27,8; 8,9) mmHg (p < 0,001), at 12 month by –14,3 (–52; 25) / –7,3 (–26; 15,0) mmHg (p < 0,001). At 12 month after RDN LVM decreased by 6,9% (p = 0,015), LV mass index by 5,5 % (p = 0,020). According to MR study, subendocardial damage was detected in 100% of patients in the absence of coronary atherosclerosis. A volume of subendocardial damage signifcantly reduced by 29 % at 6 month (p = 0,031) and by 41,4% at 12 months after RDN (p = 0.008). LVM reduced signifcantly by 18,3 % (р = 0,008). LVM also reduced signifcantly in non-responder’s group at 6 month after RDN (р = 0,046). The regression of subendocardial damage correlated with the change in systolic BP at 12 months after RDN (р = 0,034). There was no signifcant correlation between LVH regression and baseline BP and its change after RDN.Conclusions. One year after RDN, LVH decreased independently from the BP change. Subendocardial damage was detected in 100% patients, regressed at 6 months after RDN and correlated with the regression of systolic BP at 12 month after the RDN.

scholarly journals Cancer Therapy-Induced Cardiotoxicity—A Metabolic Perspective on Pathogenesis, Diagnosis and Therapy

2021 ◽  
Vol 23 (1) ◽  
pp. 441
Author(s):  
Anurag Choksey ◽  
Kerstin N. Timm
Keyword(s):  
Cancer Therapy ◽  
Therapeutic Potential ◽  
Functional Decline ◽  
Cardiac Metabolism ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Damage ◽  
Ventricular Ejection Fraction ◽  
Potential Methods

Long-term cardiovascular complications of cancer therapy are becoming ever more prevalent due to increased numbers of cancer survivors. Cancer therapy-induced cardiotoxicity (CTIC) is an incompletely understood consequence of various chemotherapies, targeted anti-cancer agents and radiation therapy. It is typically detected clinically by a reduction in cardiac left ventricular ejection fraction, assessed by echocardiography. However, once cardiac functional decline is apparent, this indicates irreversible cardiac damage, highlighting a need for the development of diagnostics which can detect CTIC prior to the onset of functional decline. There is increasing evidence to suggest that pathological alterations to cardiac metabolism play a crucial role in the development of CTIC. This review discusses the metabolic alterations and mechanisms which occur in the development of CTIC, with a focus on doxorubicin, trastuzumab, imatinib, ponatinib, sunitinib and radiotherapy. Potential methods to diagnose and predict CTIC prior to functional cardiac decline in the clinic are evaluated, with a view to both biomarker and imaging-based approaches. Finally, the therapeutic potential of therapies which manipulate cardiac metabolism in the context of adjuvant cardioprotection against CTIC is examined. Together, an integrated view of the role of metabolism in pathogenesis, diagnosis and treatment is presented.

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