**1. Introduction**

Cardiovascular diseases (CVDs) remain the leading cause of death in the world [1, 2]. By the year 2020, it is estimated that nearly 40% of all deaths worldwide will be due to CVDs, more than twice the percentage of deaths from cancer [3]. In line with the 2017 Update: A Report From the American Heart Association, CVDs account for one out of every three deaths or approximately 800,000 deaths in the United States, and coronary heart disease (CHD) accounts for most deaths due to CVDs, followed by stroke (1 of 20 deaths in the United States) and heart failure (HF) [4]. CVDs are considered multifactorial conditions which affect the essential components of the circulatory system of the human body including the heart, blood vessels and blood [5]. CVDs can either be congenital or acquired throughout people's lifespan [6]. The rising incidence of such cardiovascular risk factors as unhealthy life styles (especially eating and physical inactivity), obesity, diabetes and hypertension can underlie an increase in CVDs especially coronary artery disease (CAD). The burden of chronic diseases, including CVDs, obesity, diabetes and cancers, is rapidly increasing worldwide. These non-communicable

diseases have become a major health concern and burden to mankind, not just in developed countries but also in developing countries [7]. Chronic inflammation and oxidative stress are associated with the development of various CVDs including hypertension, arrhythmias, CAD and HF. Globally, CVDs remain a leading cause of death despite the development of new drugs and novel treatments [2]. Recent data showed that the prevalence of macro-vascular complications including coronary artery disease (CAD), peripheral artery disease (PAD) and stroke is two to four times more common in people with diabetes than healthy subjects [8]. According to the Framingham Study, the frequency of CAD is twice as common in diabetic patients of both sexes [1]. Existing data highlight the complex nature of the cardiovascular system, and different signalling pathways may play various roles depending on the stages of the pathology. In order to have a better appreciation of the effect of CVDs on the increased morbidity and mortality rate, it is helpful to have a brief understanding of the physiology and pathophysiology of the cardiovascular system.
