The Drug Candidate BGP-15 Delays the Onset of Diastolic Dysfunction in the Goto-Kakizaki Rat Model of Diabetic Cardiomyopathy

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Adverse Impact of Diet-Induced Hypercholesterolemia on Cardiovascular Tissue Homeostasis in a Rabbit Model: Time-Dependent Changes in Cardiac Parameters

The present study evaluates a hypothesis that diet-related hypercholesterolemia increases oxidative stress-related burden to cardiovascular tissue, resulting in progressively increased mortality, along with deterioration of electrophysiological and enzymatic function in rabbit myocardium. New Zealand white rabbits were divided into four groups, defined as follows: GROUP I, cholesterol-free rabbit chow for 12 weeks; GROUP II, cholesterol-free chow, 40 weeks; GROUP III, chow supplemented with 2% cholesterol, 12 weeks; GROUP IV, chow supplemented with 2% cholesterol, 40 weeks. At the 12 and 40 weeks time points, animals in each of the aforementioned cohorts were subjected to echocardiographic measurements, followed by sacrifice. Significant deterioration in major outcome variables measured in the present study were observed only in animals maintained for 40 weeks on 2% cholesterol-supplemented chow, with much lesser adverse effects noted in animals fed high cholesterol diets for only 12 weeks. It was observed that rabbits receiving high cholesterol diets for 40 weeks exhibited significantly increased mortality, worsened ejection fraction and general deterioration of cardiac functions, along with increased atherosclerotic plaque formation and infarct size. Additionally, myocardium of GROUP IV animals was observed to contain lower levels of heme oxygenase-1 (HO-1) and cytochrome c oxidase III (COX III) protein relative to the controls

Anti-Atherogenic Properties of Allium ursinum Liophylisate: Impact on Lipoprotein Homeostasis and Cardiac Biomarkers in Hypercholesterolemic Rabbits

The present investigation evaluates the capacity of Allium ursinum (wild garlic) leaf lyophilisate (WGLL; alliin content: 0.261%) to mitigate cardiovascular damage in hypercholesterolemic rabbits. New Zealand rabbits were divided into three groups: (i) cholesterol-free rabbit chow (control); (ii) rabbit chow containing 2% cholesterol (hypercholesterolemic, HC); (iii) rabbit chow containing 2% cholesterol + 2% WGLL (hypercholesterolemic treated, HCT); for eight weeks. At the zero- and eight-week time points, echocardiographic measurements were made, along with the determination of basic serum parameters. Following the treatment period, after ischemia-reperfusion injury, hemodynamic parameters were measured using an isolated working heart model. Western blot analyses of heart tissue followed for evaluating protein expression and histochemical study for the atheroma status determination. WGLL treatment mediated increases in fractional shortening; right ventricular function; peak systolic velocity; tricuspidal annular systolic velocity in live animals; along with improved aortic and coronary flow. Western blot analysis revealed WGLL-associated increases in HO-1 protein and decreases in SOD-1 protein production. WGLL-associated decreases were observed in aortic atherosclerotic plaque coverage, plasma ApoB and the activity of LDH and CK (creatine kinase) in plasma. Plasma LDL was also significantly reduced. The results clearly demonstrate that WGLL has complex cardioprotective effects, suggesting future strategies for its use in prevention and therapy for atherosclerotic disorders

A Microsurgical Arteriovenous Malformation Model on Saphenous Vessels in the Rat

Arteriovenous malformation (AVM) is an anomaly of blood vessel formation. Numerous models have been established to understand the nature of AVM. These models have limitations in terms of the diameter of the vessels used and the impact on the circulatory system. Our goal was to establish an AVM model that does not cause prompt and significant hemodynamic and cardiac alterations but is feasible for follow-up of the AVM’s progression. Sixteen female rats were randomly divided into sham-operated and AVM groups. In the AVM group, the saphenous vein and artery were interconnected using microsurgical techniques. The animals were followed up for 12 weeks. Anastomosis patency and the structural and hemodynamic changes of the heart were monitored. The hearts and vessels were histologically analyzed. During the follow-up period, shunts remained unobstructed. Systolic, diastolic, mean arterial pressure, and heart rate values slightly and non-significantly decreased in the AVM group. Echocardiogram results indicated minor systolic function impact, with slight and insignificant changes in aortic pressure and blood velocity, and minimal left ventricular wall enlargement. The small-caliber saphenous AVM model does not cause acute hemodynamic changes. Moderate but progressive alterations and venous dilatation confirmed AVM-like features. The model seems to be suitable for studying further the progression, enlargement, or destabilization of AVM

Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function in Zucker Diabetic Fatty Rats

The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH), in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF) rats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose tolerance (OGTT). Echocardiography was conducted and, following sacrifice, the effects of treatment on ischemia/reperfusion cardiac injury were assessed using the isolated working heart method. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was measured to evaluate levels of oxidative stress, and force measurements were performed on isolated cardiomyocytes to determine calcium sensitivity, active tension and myofilament co-operation. Vascular status was also evaluated on isolated arterioles using a contractile force measurement setup. The echocardiographic parameters ejection fraction (EF), fractional shortening (FS), isovolumetric relaxation time (IVRT), mitral annular plane systolic excursion (MAPSE), and Tei-index were significantly better in the MSH-treated group compared to ZDF controls. Isolated working heart aortic and coronary flow was increased in treated rats, and higher Hill coefficient indicated better myofilament co-operation in the MSH-treated group. We conclude that MSH improves global heart functions in ZDF rats, but these effects are not related to the vascular status

Cardioprotective Role of BGP-15 in Ageing Zucker Diabetic Fatty Rat (ZDF) Model: Extended Mitochondrial Longevity

Impaired mitochondrial function is associated with several metabolic diseases and health conditions, including insulin resistance and type 2 diabetes (T2DM), as well as ageing. The close relationship between the above-mentioned diseases and cardiovascular disease (CVD) (diabetic cardiomyopathy and age-related cardiovascular diseases) has long been known. Mitochondria have a crucial role: they are a primary source of energy produced in the form of ATP via fatty acid oxidation, tricarboxylic acid (TCA) cycle, and electron transport chain (ETC), and ATP synthase acts as a key regulator of cardiomyocyte survival. Mitochondrial medicine has been increasingly discussed as a promising therapeutic approach in the treatment of CVD. It is well known that vitamin B3 as an NAD+ precursor exists in several forms, e.g., nicotinic acid (niacin) and nicotinamide (NAM). These cofactors are central to cellular homeostasis, mitochondrial respiration, ATP production, and reactive oxygen species generation and inhibition. Increasing evidence suggests that the nicotinic acid derivative BGP-15 ((3-piperidine-2-hydroxy-1-propyl)-nicotinic amidoxime) improves cardiac function by reducing the incidence of arrhythmias and improves diastolic function in different animal models. Our team has valid reasons to assume that these cardioprotective effects of BGP-15 are based on its NAD+ precursor property. Our hypothesis was supported by an animal experiment where ageing ZDF rats were treated with BGP-15 for one year. Haemodynamic variables were measured with echocardiography to detect diabetic cardiomyopathy (DbCM) and age-related CVD as well. In the ZDF group, advanced HF was diagnosed, whereas the BGP-15-treated ZDF group showed diastolic dysfunction only. The significant difference between the two groups was supported by post-mortem Haematoxylin and eosin (HE) and Masson’s trichrome staining of cardiac tissues. Moreover, our hypothesis was further confirmed by the significantly elevated Cytochrome c oxidase (MTCO) and ATP synthase activity and expression detected with ELISA and Western blot analysis. To the best of our knowledge, this is the first study to demonstrate the protective effect of BGP-15 on cardiac mitochondrial respiration in an ageing ZDF model

Examination of Preferences for COVID-19 Vaccines in Hungary Based on Their Properties—Examining the Impact of Pandemic Awareness with a Hybrid Choice Approach

The COVID-19 pandemic has posed a huge challenge to the world in recent years. The development of vaccines that are as effective as possible and accessible to society offers a promising alternative for addressing the problems caused by this situation as soon as possible and to restore the pre-epidemic system. The present study investigated the preferences of residents in Hungary’s second-largest city (Debrecen) for the COVID-19 vaccine. To achieve this aim, a discrete choice experiment was conducted with 1011 participants, and the vaccine characteristics included in the design of the experiment were determined by qualitative methods and a pilot survey: (1) country of origin; (2) efficiency; (3) side effect; and (4) duration of protection. During the data collection at three vaccination sites, respondents were asked to choose between three vaccine alternatives and one “no choice” option in eight decision situations. Discrete choice model estimations were performed using a random parameter logit (RPL) specification with the final model extended to include a latent variable measuring pandemic awareness. The results showed that the vaccine with a Chinese country of origin is the least preferred among the respondents, while the Hungarian and the European vaccines are the most preferred. Furthermore, the increase in the vaccine efficiency level increased the respondents’ sense of utility for the vaccine; the short-term side effect was preferred to the long-term one; and the increase in the duration of protection provided by the vaccine increased the respondents’ sense of utility for the vaccine. Based on the parameter estimated for the latent variable, it can be concluded that as the level of pandemic awareness (which is more positive among people with chronic diseases and less important among health workers) increases, the choice of a vaccine option becomes more preferred among respondents compared to the “no choice“. The results of our investigation could contribute towards increasing compliance in the case of the vaccination-rejecting population, not only for COVID-19, but for any kind of vaccination procedure