**2. Platelet adhesion at the site of endothelial injuries**

Blood is flowing to maintain homeostasis inside the human body. Blood cells have specific functions: erythrocytes bring oxygen to tissues, leukocytes protect from infection, and platelets stop bleeding promptly. As shown in **Figure 1**, large and heavy erythrocytes tend to be located in the center of blood flow. Small cells of platelets circulate interacting with endothelial cells [11]. In the case where endothelial cells have a physiological function, platelets do not interact with them [12]. Platelets collide with the vessel wall and promptly go back to the blood flow without platelet activation. On the other hand, when endothelial cell function was disturbed by physical or chemical stimuli, endothelial cells lose their ability to keep antithrombotic function. Then, platelets immediately start the interaction with endothelial cells [12]. At the time, von Willebrand factor (VWF) is expressed on the cell surface of stimulated endothelial cells. Platelets capture VWF through glycoprotein (GP)Ibα. GPIbα is expressed on the surface

#### **Figure 1.**

*Role of erythrocytes and blood flow in platelet adhesion at the site of endothelial injury. This figure demonstrates the three-dimensional distribution of erythrocytes, platelets, and endothelial cells. Erythrocytes accumulate in the center of blood flow by biorheological effects. Accordingly, platelets circulate close to endothelial cells. In the presence of normally functioning endothelial cells, platelets do not adhere nor are activated, but just return to blood flow (panel A). If the endothelial cell function was disturbed by various stimulations, platelets are adhered and activated through their interaction with von Willebrand factor (VWF).*

**59**

**Figure 2.**

*force generated between VWF and GPIbα.*

*Mechanism of Thrombus Formation in Regard to Diet DOI: http://dx.doi.org/10.5772/intechopen.92382*

ity of platelet [23, 24].

water molecules.

of platelet regardless if they are activated or not [13]. Thus, initial adhesion of platelets at the site of endothelial cell damage occurs predominantly as a physical phenomenon, which occurs immediately without time-consuming biological process. Historically, the vast majority of vessel damage is caused by trauma. Rapid accumulation of platelets at the site of endothelial injury plays an impor-

The potential impact of erythrocytes for the onset and growth of thrombosis has first caught the interest of researchers in the 1960s [14]. Biorheological axial accumulation of flowing platelets was also recognized at the same time [15]. Clinical studies also support the notion that higher hematocrit values are related to higher risk of thrombotic diseases such as myocardial infarction [16]. These results strongly suggest the biophysical role of erythrocytes for thrombus formation. These rheological effects could hardly be controlled by food intake. In another aspect, erythrocytes also influence the function of platelet with biochemical modulation [17–19]. Indeed, erythrocytes are a huge source of ADP [20], which is one of the most potent platelet-stimulating agents [21, 22]. There is potential effects of food intake for influencing erythrocytes components which can influence thrombogenic-

Recent advances in computer technology allowed us to predict the structure and function of VWF bound with GPIbα from the physical movement of atoms and water molecules [25, 26]. By the method, physical force generated by VWF binding with GPIbα could be predicted. Platelet adhesion at injured vessel wall is summarized in **Figure 2**. Platelets are cells with a diameter of approximately 5 μm. But, when platelet adhered at the site of vessel damage, only part of platelet bound with VWF. Molecular dynamic prediction revealed that single bond of VWF and GPIbα could generate binding force approximately 70 pN [25]. Fluid dynamic force applied to platelets reaches to a couple hundred pN when the cell receives detaching force from arterial blood flow. Theoretically, several bonds between VWF and GPIbα are enough to stop platelets from adhering to the vessel wall. The mechanism of thrombus formation is a complicated process, but platelet adhesion under blood flow condition could now be constructed from physical movement of atoms and

*Platelet adhesion at the site of endothelial damage under blood flow conditions. Platelet adhesion is mediated exclusively by its glycoprotein (GP)Ibα binding with von Willebrand factor (VWF). Adhered platelets receive fluid dynamic force, but platelets continue to adhere until the detaching force becomes larger than the binding* 

tant role to keep our blood in our vessel system for surviving.

### *Mechanism of Thrombus Formation in Regard to Diet DOI: http://dx.doi.org/10.5772/intechopen.92382*

*New Insights into Metabolic Syndrome*

venous thrombosis [9].

syndrome.

registries also confirm that these risk factors are contributing factors for the recurrence of cardiovascular events [7]. Moreover, international registries also suggested these parameters as risk factors of venous thrombosis [8]. These clinical observations suggested the presence of common pathways for the onset of arterial and

The Framingham registry suggested the contributory role of obesity and less exercise as the predictors for future prevalence of risk factors. These abnormalities represented as visceral obesity-related syndrome is named as "metabolic syndrome." In metabolic syndrome patients, insulin resistance is one of the major contributors [10]. Increased body weight, high blood pressure, and dyslipidemia are common manifestations of metabolic syndrome. Long-term exposure to a highcalorie diet and lack of good exercise are supposed as underlining mechanisms for the onset of metabolic syndromes. The risk of thrombotic disease including arterial and venous thrombosis is speculated to be high in patients with metabolic

Blood is flowing to maintain homeostasis inside the human body. Blood cells have specific functions: erythrocytes bring oxygen to tissues, leukocytes protect from infection, and platelets stop bleeding promptly. As shown in **Figure 1**, large and heavy erythrocytes tend to be located in the center of blood flow. Small cells of platelets circulate interacting with endothelial cells [11]. In the case where endothelial cells have a physiological function, platelets do not interact with them [12]. Platelets collide with the vessel wall and promptly go back to the blood flow without platelet activation. On the other hand, when endothelial cell function was disturbed by physical or chemical stimuli, endothelial cells lose their ability to keep antithrombotic function. Then, platelets immediately start the interaction with endothelial cells [12]. At the time, von Willebrand factor (VWF) is expressed on the cell surface of stimulated endothelial cells. Platelets capture VWF through glycoprotein (GP)Ibα. GPIbα is expressed on the surface

*Role of erythrocytes and blood flow in platelet adhesion at the site of endothelial injury. This figure demonstrates the three-dimensional distribution of erythrocytes, platelets, and endothelial cells. Erythrocytes accumulate in the center of blood flow by biorheological effects. Accordingly, platelets circulate close to endothelial cells. In the presence of normally functioning endothelial cells, platelets do not adhere nor are activated, but just return to blood flow (panel A). If the endothelial cell function was disturbed by various stimulations, platelets are adhered and activated through their interaction with von Willebrand factor (VWF).*

**2. Platelet adhesion at the site of endothelial injuries**

**58**

**Figure 1.**

of platelet regardless if they are activated or not [13]. Thus, initial adhesion of platelets at the site of endothelial cell damage occurs predominantly as a physical phenomenon, which occurs immediately without time-consuming biological process. Historically, the vast majority of vessel damage is caused by trauma. Rapid accumulation of platelets at the site of endothelial injury plays an important role to keep our blood in our vessel system for surviving.

The potential impact of erythrocytes for the onset and growth of thrombosis has first caught the interest of researchers in the 1960s [14]. Biorheological axial accumulation of flowing platelets was also recognized at the same time [15]. Clinical studies also support the notion that higher hematocrit values are related to higher risk of thrombotic diseases such as myocardial infarction [16]. These results strongly suggest the biophysical role of erythrocytes for thrombus formation. These rheological effects could hardly be controlled by food intake. In another aspect, erythrocytes also influence the function of platelet with biochemical modulation [17–19]. Indeed, erythrocytes are a huge source of ADP [20], which is one of the most potent platelet-stimulating agents [21, 22]. There is potential effects of food intake for influencing erythrocytes components which can influence thrombogenicity of platelet [23, 24].

Recent advances in computer technology allowed us to predict the structure and function of VWF bound with GPIbα from the physical movement of atoms and water molecules [25, 26]. By the method, physical force generated by VWF binding with GPIbα could be predicted. Platelet adhesion at injured vessel wall is summarized in **Figure 2**. Platelets are cells with a diameter of approximately 5 μm. But, when platelet adhered at the site of vessel damage, only part of platelet bound with VWF. Molecular dynamic prediction revealed that single bond of VWF and GPIbα could generate binding force approximately 70 pN [25]. Fluid dynamic force applied to platelets reaches to a couple hundred pN when the cell receives detaching force from arterial blood flow. Theoretically, several bonds between VWF and GPIbα are enough to stop platelets from adhering to the vessel wall. The mechanism of thrombus formation is a complicated process, but platelet adhesion under blood flow condition could now be constructed from physical movement of atoms and water molecules.

#### **Figure 2.**

*Platelet adhesion at the site of endothelial damage under blood flow conditions. Platelet adhesion is mediated exclusively by its glycoprotein (GP)Ibα binding with von Willebrand factor (VWF). Adhered platelets receive fluid dynamic force, but platelets continue to adhere until the detaching force becomes larger than the binding force generated between VWF and GPIbα.*

It is of particular importance that endothelial damage is not caused only by acute physical or chemical stimulation. In the recent era, human beings enjoy longer life than those who lived hundreds of years ago. Just like carrying human being, vessel system become old when people become old. Longer time exposure of vessel wall to atherogenic lipids such as LDL cholesterol and its related local biological reaction causes atherosclerosis [27, 28]. Antithrombotic potential of endothelial cell in patients with atherosclerosis is reduced when compared to younger normal ones. Moreover, plaque rupture exposes subendothelial thrombotic materials to vessel lumen. Thus, atherothrombotic events occur frequently [29] in the era of aging society. The initial event resulting in symptomatic atherothrombosis is always platelet adhesion at the site of endothelial injury.

By understanding the mechanism of atherosclerosis and atherothrombosis, it is rather easy to understand that various types of food intake influence the risk of thrombosis. As regards nutritional factor, there is a hot discussion concerning cholesterol. Some suggested potential benefit of cholesterol restriction for prevention of atherothrombosis. The other suggest there are no relationship between daily cholesterol intake and the risk of atherothrombotic event risk.
