**2. Cardiovascular system physiology and pathophysiology**

The cardiovascular system (CVS) is composed of the blood, heart and blood vessels. The heart is a relentless muscular organ, which never stops pumping blood during life. It beats approximately 100,000 times per day, and each beat requires a vast amount of energy. The weight of the human heart is around 250–300 g for adult and a size similar to a closed fist. The heart rests on the diaphragm, near the midline of the thoracic cavity, and is surrounded by a fibrous sac called the pericardium [9]. The heart is divided into left and right sides by a septal wall. Each side of the heart is made up of two chambers, the atria and ventricles which are separated by atrioventricular valves [9]. The left side of the heart delivers oxygen-rich blood to the body passing through the aortic valve to the aorta (systemic circulation), while the right side pumps blood to the lungs passing though the pulmonary valve and the pulmonary artery for oxygen replenishment in the lungs (pulmonary circulation). The four valves of the heart ensure unidirectional flow of blood through the heart. The valves are opened and closed due to pressure differences between the heart chambers. The right atrium receives deoxygenated blood from the body through the superior and inferior vena cavae, while the left atrium receives oxygenated blood from the lungs through pulmonary veins. Coronary arteries supply the myocardium with oxygenrich blood (the left anterior descending coronary artery, the left circumflex artery and the right coronary artery). The apex of the heart is the pointed end, and the area opposite the apex is called the base of the heart [10]. HF develops when the volume of blood pumped from the heart is inadequate to meet the metabolic demands or needs of the body [11]. The traditional hemodynamic hypothesis is that diseases, which normally increase the hemodynamic burden of the heart, ultimately lead to HF by inducing defects in the contractility of cardiac myocytes. The hypothesis of depressed cardiac myocyte contractility in HF is in support of several other related studies [12, 13], but not all [14]. Previous investigations suggested that cardiac myocytes in the failing human heart undergo many alterations which result in a significant loss of contractile function. These alterations involved a reduction in α-myosin heavy chain gene expression along with a rise in β-myosin heavy chain gene expression, significant loss of myofilaments in myocytes and changes in cytoskeletal proteins [15].

There is general agreement about the contractile properties of the myocardium, which can be similar in both normal and in failing heart muscle under basal conditions. However, the rate-related contractile reserve is absent or significantly reduced in failing human myocardium [16]. Many studies reported that during the

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*Inflammation and Diabetic Cardiomyopathy DOI: http://dx.doi.org/10.5772/intechopen.88149*

ing conditions [19].

**3. Inflammation**

end-stage of HF, basal contractility is well preserved, but the ability to increase contractility with heart rate or sympathetic stimulation is severely depressed [17]. Thus, the fundamental changes in muscle performance and regulation can be explained by the poor pumping function, reduced exercise capacity and tachycardia intolerance of the human failing heart [14]. HF can no longer be considered a simple contractile disorder or a disease of the heart alone [18]. Clinical manifestations are, in fact, the result of changes to the cellular, sub-cellular and molecular components of the heart and to mediators that drive homeostatic control mechanisms. Cardiac remodelling (CR) is now generally accepted as a determinant of the clinical course of HF. CR is defined as genome expression, resulting in molecular, cellular and interstitial changes, and manifested clinically as changes in size, shape and function of the heart. CR is determined by the general process of adaptation, which allows for both the myocyte and the collagen network to adapt to new work-

Inflammation is one of the body's defence mechanisms, and there are commonly two types of inflammation, namely, acute and chronic inflammation. Acute inflammation starts rapidly and becomes more severe in a short time, and the symptoms may last for a few days. On the other hand, chronic inflammation which is a longterm inflammation in nature can last for prolonged periods of several months to years. Generally, the extent and effects of chronic inflammation vary with the cause of the injury and the ability of the body to repair and overcome the damage [4]. This review now describes the relevant data about inflammation induced by several risk factors leading to the onset of CVDs. Basically, an inflammatory response aims to reduce the agent that causes tissue injury and to induce appropriate wound healing and to restore tissue homeostasis [20]. A cascade of inflammatory pathways and mechanistic effects are supposedly well-orchestrated by the immune system in order to eradicate the causative agent. Several immune cells can change their number, morphology and nature depending on the stage and type of inflammation [20], provided that the immune response succeeds in repairing the initial tissue injury. However, in cases where the inflammation fails to resolve, the tissue injury, due to the persistence of the triggering agent(s) or due to unsuccessful repair of the initial tissue injury or dysfunction, a sustained underlying inflammatory process can develop, leading to further tissue dysfunction and detrimental consequences [21]. Several traditional and emerging risk factors are thought to influence the cardiovascular system especially inflammation-related chronic diseases, by their interrelation with underlying molecular and cellular manifestations. In turn, these can result in chronic inflammatory responses leading to the loss of tissue properties and subsequently dysfunction [22]. Apart from dyslipidaemia, other well-established risk factors are involved in the process including hypertension, diabetes and obesity. Inflammation that causes endothelial dysfunction seems to be the key causative underlying mechanistic player, at the molecular and cellular levels, for the onset and development of subsequent inflammation-related chronic disorders such as atherosclerosis and subsequent CVDs and renal disorders [23, 24]. Hypertension, diabetes and obesity have harmful effects of oxidised low-density lipoprotein cholesterol, initiating a chronic inflammatory reaction, the result of which is a vulnerable plaque, prone to rupture and thrombosis. Epidemiological and clinical studies have shown strong and consistent relationships between markers of inflammation and risk of future cardiovascular events [3]. Inflammation is widely considered to be an important contributing factor in atherogenesis and the risk

#### *Inflammation and Diabetic Cardiomyopathy DOI: http://dx.doi.org/10.5772/intechopen.88149*

end-stage of HF, basal contractility is well preserved, but the ability to increase contractility with heart rate or sympathetic stimulation is severely depressed [17]. Thus, the fundamental changes in muscle performance and regulation can be explained by the poor pumping function, reduced exercise capacity and tachycardia intolerance of the human failing heart [14]. HF can no longer be considered a simple contractile disorder or a disease of the heart alone [18]. Clinical manifestations are, in fact, the result of changes to the cellular, sub-cellular and molecular components of the heart and to mediators that drive homeostatic control mechanisms. Cardiac remodelling (CR) is now generally accepted as a determinant of the clinical course of HF. CR is defined as genome expression, resulting in molecular, cellular and interstitial changes, and manifested clinically as changes in size, shape and function of the heart. CR is determined by the general process of adaptation, which allows for both the myocyte and the collagen network to adapt to new working conditions [19].
