Advancements in Cardiovascular Research and Therapeutics: Molecular and Nutraceutical Perspectives

Food and nutrients are essential for the body's regular functioning. They aid in the preservation of an individual's health and the reduction of the danger of certain diseases. As a result of the widespread recognition of this fact, a link was established between “nutrition and health,” and the term “nutraceuticals” was coined. Nutraceuticals are therapeutic foods that aid in maintaining well-being, enhancing health, regulating immunity, and preventing as well as curing certain diseases. Nutraceuticals might thus be thought of as one of the missing pieces in a person's overall health. More than any other illness, cardiovascular disease has numerous risk variables that are susceptible to nutraceutical treatment. It is critical to see nutraceuticals' ability to improve cardiovascular risk factors as a huge opportunity in the treatment of a disease that affects so many people. Nutraceuticals show promise in clinical treatment since they have the potential to minimize the risk of chemotherapyrelated side effects while also lowering the overall cost of health care. In this study, an attempt was made to summarize some of the most recent research findings on garlic, omega-3 fatty acids, soy products, dietary fibers, vitamins, antioxidants, plant sterols, flavonoids, prebiotics, and probiotics that have beneficial effects on the heart, as well as to provide insight into a bioinformatics approach to identify novel therapeutic biomarkers in order to keep practitioners up to date.

Congestive Heart Failure (CHF) is the inability of the heart to supply blood to other organs and tissues to meet its need for metabolism. Over 64.3 million people around the world live with heart failure. Some of the common causes of CHF include myocardial infarction, increase in blood pressure, atrial fibrillation and cardiomyopathy. The complete etiology of CHF is complex. Patients with HF often experience fatigue, dyspnea, and pain, lack of energy, cognitive impairment and depression. Left ventricular ejection fraction (LVEF) is a measure of the amount of blood pumped from the heart's left ventricle during each contraction. It is used as a phenotypic marker in the indication of the pathophysiological mechanism and sensitivity to therapy. The pathogenesis of HF with low ejection fraction is that of a progressive state. The various classes of drugs used clinically for the treatment of congestive heart failure are diuretics, beta blockers, ACE inhibitors and vasopressin receptor antagonists. The management of Heart failure includes acute decompensation, chronic management and palliative care. Cardiac glycosides are a varied group of naturally obtained compounds used in the treatment of CHF. They exhibit their action by binding to and inhibiting Na+/K+-ATPase. Then, they consequently increase the force of myocardial contraction. The primary structure of these drugs is a steroidal framework, which is the pharmacophoric component that is responsible for their activity. The most familiar cardiac glycosides are digitoxin, digoxin, oleandrin, bufalin, ouabain, marinobufagenin, telocinobufagin and aerobufagenin. Among other cardiac glycosides, digoxin has been proven to improve symptom alleviation, functional capacity, quality of life and exercise tolerance in patients with mild to moderate HF in clinical trials. Early detection and prevention interventions, as well as lifestyle changes, are essential.

Diet has been implicated in cardiovascular inflammation and the development of cardiovascular disorders. Several studies have correlated the dietary pattern with cardiovascular disease incidences. Especially high carbohydrate diet consists of refined starches, sugar, and saturated and trans-fatty acids shown to cause vascular inflammation and its related CVDs. To modify or prevent CVD complications, studies have highlighted and recommended a dietary pattern rich in protein and fibers with low carbohydrates. However, the long term effects of these low carbohydrate diets have not been analysed. Further, the diet consumed in Asian countries is rich in spices and they are loaded with antioxidants. Hence, this has to be reviewed thoroughly to conclude on the role of antioxidants in preventing CVDs. Therefore, in this chapter diet-induced inflammation, the role of low carbohydrate and high fat/protein diets in preventing vascular inflammation and their long term effects on health and the usefulness of antioxidants in preventing cardiovascular diseases will be reviewed elaborately.

Cardiovascular diseases (CVD) come under non-communicable disease (NCD) that are responsible for the leading cause of death, globally. They involve a range of pathologies viz. coronary artery disease, cerebro-vascular disease, venous thrombo-embolism, peripheral vascular disease, myocardial infarction, cardiac arrhythmias and stroke. Each pathology is the result of the complex interplay of many factors which determine the prognosis of the condition. Animal experimentation has played an important role in the fundamental understanding of pathologies of cardiac diseases and discovered improved methods of diagnosis and treatment. Researchers have used a number of lab animals that involve rodents (mice, rats, hamsters, and rabbits) and non-rodent animal models (dogs, pigs, sheep, primates) as a biological system to mimic cardiovascular diseases for translational research. An ideal animalmodel system should be cheap, readily manipulable, reproducible, ethically sound and reflect the complexity of cardiovascular diseases. Rodent animal models are considered the prime model for human research. Common rodent models include mice, rats and hamsters; rabbits are used for studies on cardiac hypertrophy, heart failure, aortic constriction, pulmonary vein constriction, atherosclerosis and cholesterol regulation studies. With the advancement in genetic engineering, several transgenic/humanized rodent models are available which can mimic better human systems for translational application. Among non-rodent animal models, pigs, dogs, sheep, and non-human primates serve as an excellent model in cardiovascular research; owing to the similarity in heart structure, atrio-ventricular valves, lipid metabolism and vasculature with humans. In the current chapter, we will deal with the importance of the models and their characteristic features, advantages and limitations.

21st Century Genome-editing technologies have been rapidly emerging as the most powerful tool capable of creating genetically altered cells or organisms for explicit gene functions and mechanisms for causing several human ailments. While clinical gene therapy celebrates its first taste of success, with several products approved for clinical usage and several thousands of them awaiting stages in pipelines, unfortunately, there are no gene therapy treatment methods available for many cardiovascular diseases (CVD). Despite sustained medical advances over the last 50 years in CVD, the main cause of death is still uncertain in the developed world. The management of genetic expression by using small molecule RNA therapeutics and the development of accurate gene corrections may lead to several applications, such as cardiac revitalization after myocardial infarctions and gene corrections for the inherited cardiomyopathies but certainly with some limitations. CRISPR/Cas9 technology can be utilized to realign DNA modifications ranging from a single base pair to multiplepairs of mutations in both in vitro and in vivo models. This book chapter emphasizes various types of applications by CRISPR technologies in cardio-vascular research, and genome-editing novel therapies for future medicines.

A systems approach to health is the hallmark of Ayurveda. It believes in preventing disease and maintaining and restoring health. The entire concept stands on three fundamental functional units-Vata, Pitta and Kapha, where Vata, mobilizes the other two units. Depending on their locations, Vata (Vayu) is classified into five subtypes, where each has its distinct role to perform. Vyana Vayu (VV), an important subtype of Vata, is synthesized in myocytes and responsible for the genesis of the action potential. A key regulator in contractile functions, VV propels out nutrients from the heart. It not only mediates intracrine and paracrine activities but modulates the vascular tone too. Wherever there is scope to flow, VV has its unique role to contribute. Ancient scholars of Ayurveda have identified its ubiquitous role in the endogenous system, where all the activities depend on VV. Hence, preventing VV from any stimulus is of paramount importance since they consequently lead to various cardio vascular diseases (CVD). Classical texts have addressed the prognosis in six discrete phases where each phase can be avoided strategically. Highlighting the precipitants that attenuate VV, we focus on addressing those phases along with curative measures so that the functions of Vyana Vayu can be restored.

Cardiovascular disease(CVD) is the foremost global health problem that accounts for the highest rate of morbidity, mortality and huge healthcare costs. Food habits and lifestyles predominantly affect the functioning of the cardiovascular system either directly or indirectly through risk factors like hypertension, obesity, dyslipidemia, diabetes, etc. Decreased physical activity, increased sedentariness, and growing fast food culture are some of the apparent reasons that make the disease impact more on the younger generation. Several plant species have been reported in ethnomedicine for their therapeutic efficacies against CVDs and other diseases. Even though some preclinical and clinical studies have demonstrated the beneficial effects of dietary plant components in the prevention and treatment of CVDs, they are limited to selected study groups. Therefore, their scope and utility need to be broadened and applied to larger populations to reduce the public health burden of CVDs. Since nutraceutical approach is more preferable than other therapeutic methods, there is a growing interest in functional foods and diet based remedies. In the present chapter, we have presented the current scenario of CVDs, their pathophysiology, the therapeutic drugs available, the role of nutraceuticals in treating CVDs and their mode of action with a special emphasis on commonly used kitchen spices.

In this study, we made an attempt to attenuate the dexamethasone induced hypertension through Biochanin-A (BCA) in experimental rats. Hypertension was induced in male albino Wistar rats by subcutaneous administration of dexamethasone (10μg/kg body weight). The rats were orally treated with BCA (10mg/kg body weight) once daily for 45 days and Nicorandil-treated group (6mg/kg body weight) included for comparison. We evaluated the changes in mean arterial pressure, heart rate, blood pressure, vascular function, oxidative stress markers, and gene expression of histone deacetylases (HDAC)-1, HDAC-2, and HDAC-8. Administration of BCA or Nicorandil showed noteworthy improvement in vascular function in experimental rats. Moreover, aortic eNOS expression was down regulated, and NADPH oxidase subunit p47phox was up regulated in hypertensive rats. The antihypertensive effects of BCA were connected with concomitant downregulation of p47phox expression and upregulation of eNOS expression. Dexamethasone exposure led to increased mRNA expression of HDACs expression in the kidneys and these were restored after BCA administration. In conclusion, our results are, therefore, BCA reduces hypertension in experimental rats and suggests that BCA might be used against the hypertension.

In the current study, we evaluated the effect of Zingiberene (ZB) is, a monocyclic sesquiterpene that is the principal constituent of ginger (Zingiber officinale), against high-fat-diet (HFD)-induced obesity cardiomyopathy (OC) in rats. ZB (50mg/kg/BW) was supplemented on obese rats for the period of 45 days and assessed its effect of body weight, anthropometrical and morphological parameters along with hyperglycemic markers. We also evaluated the effect of ZB on cardiac lipotoxicity and oxidative stress in cardiac tissue. The current study demonstrated that HFD supplementation significantly increased body weight, anthropometrical and morphological parameters, together developed hyperglycemia in rats. On the other hand, ZB supplementation in obese rats attenuated these altered parameters and ameliorated cardiac lipotoxicity as well as oxidative stress by decreasing lipid profiles of heart and enhancing the activities of endogenous antioxidant enzymes in the heart. Therefore, this study suggest that ZB might ameliorate the diet induced OC through the restoration of antioxidant system of the heart and attenuation of dyslipidemia in the cardiac.

Cardiovascular disease is a key community health challenge and presently the condition with the utmost deaths around the globe, even though enormous development has been made in its management but there are still many difficulties. In the current study, we made an attempt to evaluate the therapeutic action of betaine, an active nutraceutical against isoproterenol-induced myocardial infarction (MI) in rats. The rats were pre-treated with betaine (250mg/Kg BW) for the period of 30 days and on the 31st and 32nd days, they were administered with isoproterenol (20mg/Kg BW) to produce MI in rats. Then we evaluated the effects of betaine on the ratio of heart weight to the body weight. Cardiac diagnostic markers and the production of proinflammatory cytokines and matrix metallopreoteinases along with their mRNA expressions were also studied in the heart by RT-PCR. We found that there was a significant elevation in the heart size, levels of LDH, CK-MB, CRP, homocysteine and serum pro-inflammatory cytokines (TNF-ɑ, IL-1ɑ, IL-1β, IL-6, MCP-1 and RANTES) and matrix metallopreoteinases (MMP-2 and MMP-9) in MI rats. On the other hand, pre-treatment of MI rats with betaine revealed a noteworthy reduction in the proinflammatory cytokines and matrix metallopreoteinases in the serum. RT-PCR study revealed that betaine successfully down-regulated the mRNA expressions of NF-κB, TNF-ɑ, IL-6, MMP-2 and MMP-9 in MI rats. In conclusion, this study revealed that betaine is able to ameliorate MI by restraining the production of pro-inflammatory cytokines and matrix metallopreoteinases. Hence, betaine might be used as a dietary supplement as an alternative for cardio-protection.