Effects of High Cholesterol and Saturated Fat Diet on the Aortic Wall Structure of New Zealand White Male Rabbits

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1 Saudi Journal of Biological Sciences 14 (2) December, 2007 ISSN X The Official Journal of the Saudi Biological Society htt: Effects of High Cholesterol and Saturated Fat Diet on the Aortic Wall Structure of New Zealand White Male Rabbits Mohamed Anwar K Abdelhalim and Mohamed S. Al-Ayed King Saud University, Faculty of Science, Department of Physics and Astronomy, Biomedical Science group, Riyadh, Saudi Arabia abdelhalimmak@yahoo.com, Phone: , Fax: Abstract There has been increased attention focused on atherosclerosis, with a rise in the number of investigations exploring its pathogenesis and ways of diagnosing and treating the disease. During the progression and development of atherosclerosis, the mechanical properties of the arterial wall have been extensively studied using animals fed a diet of high cholesterol and saturated fat. One view held is that the arterial wall becomes hardened, while others hold the opposite view. From the standpoints of diagnosis and treatment, dimensional and morphological changes in the arterial wall during the development of atherosclerosis are considered to play important roles. However, the dimensional and morphological changes in the arterial wall of animals fed a high cholesterol and saturated fat diet have not been well documented. Therefore, in this study, rabbits were fed a diet containing 0.5% cholesterol plus 0.5% olive oil for periods of 4, 8, and 12 weeks, and the cholesterol concentration of blood plasma, and the dimensional and morphological changes in the rabbit s arterial wall were examined following each cholesterol feeding period. We found that the cholesterol concentration of blood plasma significantly increased throughout the cholesterol feeding period. In cholesterolfed rabbits, the arterial wall had a tendency to thicken; the ratio of wall thickness to radius of aortic ring specimens, measured immediately after procurement of the specimen, was significantly increased compared with normal-fed rabbits. Morphological examination revealed a marked increase in thickness of the intima, smooth muscle proliferation, and connective tissue formation; lipid-laden cells were observed near the basement of the lesion. The tunica media underlying plaques showed marked disruption of elastin, collagen, smooth muscle cells, and a focal loss of normal media architecture. These changes were noted to be more prominent in thoracic aortae than in abdominal aortae. Key words: arterial wall morphology; arterial wall thickness; atherosclerosis; cholesterol feeding periods; rabbit aorta Introduction Atherosclerosis is a disease of the large- and mediumsized arteries i.e. coronary artery, carotid artery, arteries of the lower extremities, and large elastic arteries including thoracic and abdominal aortae (Abdelhalim et al., 1994; Ross, 1993; Sato and Ohshima, 1992; Shankar and Bond, 1990; Stary, 1989). Atherosclerotic calcification may weaken the aorta wall and thereby lead to rupture of the vessel (Howard et al., 2002). Hypercholesterolemia is considered a major risk factor in the development of atherosclerotic disease (Fidan et al., 2006; Sandra, 2006). Presently, increasing numbers of the adult and geriatric populations are developing this disease. The effects of cholesterol feeding periods on the mechanical properties of excised thoracic and abdominal aortae of rabbits fed a diet containing high levels of cholesterol and saturated fat have been investigated by means of a tensile testing machine (Abdelhalim et al., 1993, 1994; Cox, 1979; Hayashi et al., 1987; Hudetz et al., 1981; Richter and Mittermayer, 1984; Sato and Ohshima, 1992; Shankar and Bond, 1990; Miyazaki This project supported by College of Science - Research Center Project Nos: Physics / 2005 / 25 and Physics / 2006 /41. Saudi Journal of Biological Sciences Vol. 14, No (2) December,

2 Mohamed Anwar K Abdelhalim and Mohamed Suleiman Alayed et al., 1983). These studies demonstrated significant changes in the mechanical properties of aortae during the development of atherosclerosis. High fat dietinduced prothrombotic state, endothelial dysfunction precedes both the morphologically detectable lesions and the enhancement of platelet reactivity (Rumiko et al., 2006). Atherosclerosis is considered to be a vascular disease accompanying fibrous thickening of the intima of the arterial wall (Badimon et al., 1989). Thus, the time course of the changes in the dimensions of blood vessels is considered to be one of the major factors in the development of atherosclerosis. The dimensional and morphological changes in the arterial wall of animals fed a high cholesterol and saturated fat diet have not been well documented. Moreover, controversy exists regarding the relevance of dimensional and morphological changes in the arterial wall to the development of atherosclerosis. In a bid to clarify this issue, we examined the cholesterol concentration of blood plasma, and the dimensional and morphological changes in the arterial wall of rabbits fed a high cholesterol and saturated fat diet throughout the cholesterol feeding period. We compared our findings with previous reports of changes in the mechanical properties of animals during the development of atherosclerosis, in particular, arterial wall thickness, the possible appearance of fatty streaks and fibrous plaques, and degenerative changes in the connective tissue matrix (collagen, elastic fibers, and proteoglycan) of the arterial wall in hyperlipidemic rabbits. Materials and Methods Animals Fifteen 12 - week, new Zealand White male rabbits, old, were purchased from Kitayama Lab. Ltd., Kyoto, Japan, individually caged, and divided into either control group or cholesterol-fed group. The control group (n = 6) was fed 100 g/day of normal diet, ORC-4 (Oriental Yeast Co. Ltd., Tokyo, Japan), for a feeding period of 12 weeks. The cholesterol-fed group (n = 9) was fed a high cholesterol and saturated fat diet of ORC-4 containing 0.5% cholesterol plus 0.5% olive oil (100 g/day), for a feeding period of 12 weeks. Experimental protocol Rabbits were sacrificed following intravenous injection of heparin (400 U/kg body weight). To obtain protoplasm representative of the in vivo situation, and to avoid autolysis changes and bacterial growth, the aortae were placed in 10% buffered neutral formalin. The tissues surrounding the aortae and their branched vessels were carefully removed in a manner which avoided any damage to the aortae. According to routine procedures, specimens were stained to examine fatty streaks, fibrous plaques and any degenerative changes in the arterial wall. The thoracic aorta (2 cm under the bifurcation to the left sub-clavian artery) and abdominal aorta (1 cm upward and downward from the bifurcation to the mesenteric artery) were excised. Between two and four pieces of ring specimens, approximately 2-3 mm in width, were excised from each part of the thoracic and abdominal aortae. The internal diameter, thickness, and width of each aortic specimen were measured under a stereo microscope. Morphological examination To investigate the possible presence of fatty streaks and fibrous plaques, photomicrographs of Sudan-stained aortic specimens were prepared using the whole aorta from normal-fed rabbits (NOR) and cholesterol-fed rabbits (CHO). To examine intimal thickening, focal loss of medial architecture, intima intracellular and extracellular lipids, connective tissue formation, and smooth muscle proliferation, photomicrographs of hematoxylin and eosin-stained thoracic and abdominal aortae were prepared from NOR and CHO. Furthermore, to investigate intimal thickening, focal loss of medial architecture, disruption of the elastin of tunica media, condensed and fragmented elastin near the innermost and the outermost boundary of the media, photomicrographs of Victoria blue-stained thoracic and abdominal aortae were prepared from NOR and CHO. Data analysis Statistical analysis was performed using a One- Way Analysis of Variance (ANOVA) for repeated measurements, with significance assessed at 5% confidence level. The results were expressed as mean ± SD. Results Cholesterol concentration changes The total cholesterol concentration in blood plasma 228 Saudi Journal of Biological Sciences Vol. 14, No (2) December, 2007

3 Effects of High Cholesterol and Saturated Fat Diet on the Aortic Wall of CHO increased after the cholesterol feeding started, as illustrated in Table. 1. The total cholesterol concentration at the beginning of cholesterol feeding, was 163 ± 73 mg/dl, was considered to be the control level. After cholesterol feeding started, this value rapidly and significantly ( p < 0.05) increased throughout the feeding period. After 12 weeks of cholesterol feeding, the concentration of total cholesterol in blood plasma was rose to 2111 ± 440 mg/dl, as illustrated in Fig. 1. Statistical analysis was performed using a One- Way Analysis of Variance (ANOVA) for repeated measurements, with significance assessed at 5% confidence level. The results were expressed as mean ± SD, as illustrated in Table 2. Table 2 shows total cholesterol concentration in blood plasma of normalfed rabbits (NOR), and cholesterol-fed rabbits (CHO) throughout feeding periods of 4, 8, and 12 weeks. Dimensional changes in the aortic wall As mentioned previously, atherosclerosis is considered to be a vascular disease accompanying fibrous thickening of the intima of the arterial wall (Badimon et al., 1989). Thus, the time course of the changes in the dimensions of blood vessels is considered to be one of the major factors in the development of atherosclerosis. Accordingly, the ratio of wall thickness to radius of aortic ring specimens were measured immediately after procurement of the specimen. The results obtained after cholesterol feeding periods of 4, 8, and 12 weeks are shown in Table 3. Our measurements showed that rabbits fed a diet containing a high concentration of cholesterol and saturated fat exhibited a significant ( p < 0.05) increase in the ratio of wall thickness to radius of aortic rings, resulting in a tendancy for the aortic wall to thicken. Moreover, these changes were noted to be more prominent in thoracic aortae than in abdominal aortae, as illustrated in Fig. 2. Statistical analysis using a One-Way Analysis of Variance (ANOVA) for wall thickness to radius of the thoracic and abdominal aorta of normal-fed rabbits, and cholesterol-fed rabbits throughout a feeding period of 4, 8, and 12 weeks were illustrated in Tables 4 (thoracic aorta) and 5 (abdominal aorta). Morphological changes in the aortic wall It has been proposed that softening of the arterial wall is due to the denaturation or fragmentation of elastin and collagen fibers, both of which are known to play dominant roles in governing the mechanical properties of blood vessels. The morphological changes observed in the aortic wall are illustrated in Figs. 3, 4, 5, 6 and 7. Fig. 3 is a photomicrograph of Sudan-stained whole aortae from NOR and CHO. Red stained areas correspond to the localization of fatty streaks and fibrous plaques. In panel A, the upper specimen was obtained from a rabbit fed a high cholesterol and saturated fat diet (100 g/day) for Cholesterol concentration in plasma (mg/dl) Mean ± SD (n) (NOR, n = 6) (CHO, n = 9) Feeding periods (weeks) Fig. 1 Vertical bar graph between cholesterol feeding periods in weeks and cholesterol concentration Fig 1. Vertical in blood bar plasma. graph n = between number of rabbits; cholesterol normal-fed feeding rabbits (NOR), periods cholesterol-fed rabbits (CHO) Mean ± SD ( p < 0.05). in weeks and cholesterol concentration in blood plasma. n = number of rabbits; normal-fed rabbits (NOR), cholesterolfed rabbits (CHO) Mean ± SD (p < 0.05). Ratio of wall thickness to radius (-) n= 12 (3) 0.15 n= 11 (3) Thoracic Aorta Abdominal Aorta n= 15 (4) n= 12 (4) n= 19 (5) n= 12 (5) n= 35 (8) n= 30 (8) Feeding periods (wks) Fig. 2 The changes in the ratio of wall thickness to radius of arterial wall with the Fig cholesterol 2. The feeding changes periods. in the n is ratio the number of wall of thickness samples, ( ) to is the radius number of arterial of rabbits. wall Mean with ± SD the ( P cholesterol < 0.05) feeding periods. n is the number of samples, ( ) is the number of rabbits, Mean ± SD (p < 0.05). Saudi Journal of Biological Sciences Vol. 14, No (2) December,

4 Mohamed Anwar K Abdelhalim and Mohamed Suleiman Alayed Table 1. Represents mean total cholesterol concentration in blood plasma of normal-fed rabbits (NOR), and cholesterol-fed rabbits (CHO) throughout feeding periods of 4, 8, and 12 weeks. Data Mean ± SD V N Control 163 ± Weeks 1325 ± Weeks 2046 ± Weeks ± Values are expressed as mean ± SD, followed by variance (V) and number of rabbits (N). Table 2. Statistical analysis using a One-Way Analysis of Variance (ANOVA) for total cholesterol concentration in blood plasma of normal-fed rabbits and cholesterol-fed rabbits, with significance assessed at 5% confidence level. Data (Control and 4 Weeks) Mean Variance N Control Weeks F = P = 2.78 E-9 At the 0.05 level, the means are significantly different. Data (Control and 8 Weeks) Mean Variance N Control Weeks F = P = 1.38 E-9 At the 0.05 level, the means are significantly different. Data (Control and 12 Weeks) Mean Variance N Control Weeks F = P = 1.11 E-10 At the 0.05 level, the means are significantly different. 12 weeks. In panel B, the upper specimen was obtained from a rabbit fed a high cholesterol and saturated fat diet (100 g/day) for 7 weeks followed by a lower intake of cholesterol and saturated fat (40 g/day) for 5 weeks. After 7 weeks of a high cholesterol and saturated fat diet, this animal exhibited loss of appetite. It became evident that the aortae of NOR were completely free of fatty streaks and fibrous plaques, and were characterized by a barely visible intima (Fig. 3). On the contrary, all aortic specimens from CHO exhibited lesions which comprised of fatty streaks and fibrous plaques (Fig. 3). Fig. 4 is a photomicrograph of hematoxylin and eosin-stained thoracic aortae from NOR and CHO rabbits. The upper panel (NOR) illustrates normal arterial wall morphology. The lower panel (CHO) shows marked intimal thickening with focal loss of medial architecture. The intima contains intracellular and extracellular lipids, connective tissue formation, and 230 Saudi Journal of Biological Sciences Vol. 14, No (2) December, 2007

5 Effects of High Cholesterol and Saturated Fat Diet on the Aortic Wall smooth muscle proliferation. Fig. 5 is a photomicrograph of hematoxylin and eosin-stained abdominal aortae from a NOR and a CHO. The upper panel (NOR) illustrates normal arterial wall morphology. The lower panel (CHO) shows an intima with moderately developed fatty streaks. A slight increase in intimal thickness and medial architecture were noted in CHO compared with NOR. These changes were less prominent than the ones observed with thoracic aortae. Fig. 6 is a photomicrograph of Victoria blue-stained thoracic aortae from a NOR and a CHO. The upper panel (NOR) illustrates normal arterial wall morphology. The lower panel (CHO) shows marked intimal thickening as well as a significant focal loss of medial architecture compared with the NOR specimen. In the CHO specimen, tunica media underlying plaques show a marked disruption, with loss of elastin. Less condensed and fragmented elastin was observed near the innermost and the outermost boundary of the media. Fig. 7 is a photomicrograph of Victoria blue-stained abdominal aortae from a NOR and a CHO. The upper panel (NOR) illustrates normal arterial wall morphology. The Fig 3. Photomicrograph of Sudan-stained whole aortac from NOR and CHO. Fig 6. Photomicrograph of Victoria blue-stained thoracic aortic from a NOR and a CHO. Fig 4. Photomicrograph of hematoxylin and cosin-stained thoracic aortac from a NOR and a CHO. Fig 5. Photomicrograph of hematoxylin and cosin-stained abdominal aortae from a NOR and a CHO. Fig 7. Photomicrograph of Victoria blue-stained abdominal aortae from a NOR and a CHO. Saudi Journal of Biological Sciences Vol. 14, No (2) December,

6 Mohamed Anwar K Abdelhalim and Mohamed Suleiman Alayed Table 3. Represents mean ratio of wall thickness to radius of the thoracic and abdominal aorta of normal-fed rabbits, and cholesterol-fed rabbits throughout a feeding period of 4, 8, and 12 weeks. Thoracic Aorta Data Mean ± SD V N Control ± e Weeks ± E Weeks ± E Weeks ± E-4 35 Abdominal Aorta Data Mean ± SD V N Control ± ± E Weeks ± E Weeks ± E Weeks ± E-4 29 Values are expressed as mean ± SD, followed by variance (V) and number of aortic specimens (N). Table 4. Represents the statistical analysis using a One-Way Analysis of Variance (ANOVA) for mean ratio of wall thickness to radius of thoracic aorta of normal-fed rabbits, and cholesterol-fed rabbits throughout feeding periods of 4, 8, and 12 weeks Data (Control and 4 Weeks) Mean V N Control E Weeks E-4 15 F = P = At the 0.05 level, the means are not significantly different. Data (Control and 8 Weeks) Mean V N Control E Weeks E-4 19 F = P = E-7 At the 0.05 level, the means are significantly different. Data (Control and 12 Weeks) Mean V N Control E Weeks E-4 35 F = P = E-7 At the 0.05 level, the means are significantly different. Values are expressed as mean ± SD, followed by variance (V) and number of of aortic specimens (N). lower panel (CHO) shows a slight increase in intimal thickness. Discussion In the present study, rabbits were fed a high cholesterol and saturated fat diet for periods of 4, 8, and 12 weeks, and the accompanying changes in the cholesterol concentration of blood plasma, and the dimensional and morphological changes in the arterial wall were 232 Saudi Journal of Biological Sciences Vol. 14, No (2) December, 2007

7 Effects of High Cholesterol and Saturated Fat Diet on the Aortic Wall Table 5. Represents the statistical analysis using a One-Way Analysis of Variance (ANOVA) for mean ratio of wall thickness to radius of abdominal aorta of normal-fed rabbits, and cholesterol-fed rabbits throughout feeding periods of 4, 8, and 12 weeks. Data (Control and 4 Weeks) Mean V N Control E Weeks E-4 12 F = P = 0.12 At the 0.05 level, the means are not significantly different. Data (Control and 8 Weeks) Mean V N Control E Weeks E-4 12 F = P = E-7 At the 0.05 level, the means are significantly different. Data (Control and 12 Weeks) Mean V N Control E Weeks E-4 29 F = P = E-7 At the 0.05 level, the means are significantly different. Values are expressed as mean ± SD, followed by variance (V) and number of aortic specimens (N). investigated. The total cholesterol concentration of blood plasma of CHO rapidly and significantly increased throughout the feeding period. Interestingly, it has been reported that a chronically elevated level of cholesterol is associated with an increased incidence of atherosclerosis (Sandra, 2006; Inkeles and Eisenberg, 1981). Studies found that a high cholesterol diet resulted in an elevation of the plasma level of low-density lipoprotein, and that the cholesterol was incorporated into the atherosclerotic plaques (Brown and Goldstein, 1984, 1986; Goldstein et al., 1983). Our findings strongly suggest that the increase in the cholesterol concentration of blood plasma of CHO is a major factor in the production of the significant dimensional and morphological changes in the arterial wall. Our findings also suggest that cholesterol feeding has a general tendency for thickening and softening the arterial wall of hyperlipidemic rabbits. It became evident from our results that feeding rabbits a diet containing high concentrations of cholesterol and saturated fat caused a significant increase in the ratio of wall thickness to radius of aortic ring specimens, leading to a tendancy for the aortic wall to thicken. Due to the fact that the internal diameter of each aortic specimen was not found to change significantly, the increase in the ratio of wall thickness to radius is considered to be due solely to an increase in wall thickness. Furthermore, these changes were observed to be more prominent in thoracic aortae compared with abdominal aortae. It has been suggested that this thickening of the arterial wall may be due to lipid and cholesterol deposition, proliferation of smooth muscle cells, and connective tissue matrix formation (collagen, elastic fibers, and proteoglycan) in the intima or media of the arterial wall. As mentioned previously, atherosclerosis is considered to be a vascular disease accompanying fibrous thickening of the intima of the arterial wall (Badimon et al., 1989). Atherosclerosis is characterized by one of three types of focal lesion: fatty streak, fibrous Saudi Journal of Biological Sciences Vol. 14, No (2) December,

8 Mohamed Anwar K Abdelhalim and Mohamed Suleiman Alayed plaque or complicated lesion and calcification (Kissane, 1985; Ross, 1993). Aortic calcification is considered a later event during atherogenesis (Howard et al., 2002). The fatty streak is a possible precursor of the fibrous plaque (Ross, 1993). The fibrous plaque represents the advanced form of atherosclerosis, and consists of proliferating smooth muscle cells surrounded by connective tissue. It is characterized by a fibrous cap, which covers the proliferating smooth muscle cells and leukocytes, including macrophages and lymphocytes (Ross, 1993). Endothelial dysfunction precedes both the morphologically detectable lesions and the enhancement of platelet reactivity (Rumiko et al., 2006). It has been proposed that softening of the arterial wall is due to the denaturation or fragmentation of media elastin and collagen fibers, both of which are known to play dominant roles in governing the mechanical properties of blood vessels. Indeed, the denaturation of elastin and collagen has been reported in previous studies (Fischer et al., 1980; Ooshima et al., 1988). It should be noted that investigations concerning the roles of several other potentially important factors in atherosclerosis were beyond the scope of this study, but their contributions to the disease should be considered in future work. Specifically, plasma viscosity in CHO should be examined, as an elevation in plasma viscosity is considered a predictor of atherosclerotic vascular disease, as well as a potential mechanism for increasing cardiovascular risk. Also, the plasma levels of triglyceride and fibrinogen in CHO require to be studied. Acknowledgements This study was kindly supported and supervised by Drs. T Watanabe and T Shimokama, Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Japan. This research was partly supported by a grant from College of Science, KSU Research Center Saudi Arabia, (Project No. Physics/2005/25 and Physics/2006/41, and a grant from Special Research Project on Circulation Biosystems, University of Tsukuba, Japan. References Abdelhalim, M.A.K., Masaaki, S. and Norio, O., Mechanical properties of aortae of rabbits fed a high cholesterol diet. Microcirc Annual. 9: Abdelhalim, M.A.K., Masaaki, S. and Norio, O., Effects of cholesterol feeding periods on aortic mechanical properties of rabbits. JSME. Int. J. 37: Badimon, J.J., Badimon, L., Galves, A., Dische, R. and Fuster, V., High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits. Lab Invest 60: Brown, M.S. and Goldstein, J.L., How LDL receptors influence cholesterol and atherosclerosis. Sci Am. 251: Brown, M.S. and Goldstein, J.L., A receptor-mediated pathway for cholesterol homeostasis. Science 232: Cox, R.H, Regional, species, and age related variations in the mechanical properties of arteries. Biorheology. 16: Fidan, H., Goksel, K., Zeki, K., Murat, K., and Hilimi, I., The effect of ethanol extract of hypericum lysimachioides on lipid profile in hypercholesterolemic rabbits and its in vitro antioxidant activity. Atherosclerosis in Press. Fischer, G.M., Swain, M.L. and Cherian, K., Increased vascular collagen and elastin synthesis in experimental atherosclerosis in the rabbit, variation in synthesis among major vessels. Atherosclerosis 35: Goldstein, J.L., Kita, T. and Brown, M.S., Defective lipoprotein receptors and atherosclerosis. Lessons from an animal counterpart of familial hypercholesterolemia. N. Engl. J. Med. 309: Hayashi, K., Takamizawa, K., Nakamura, T., Kato, T. and Tsushima, N., Effects of elastase on the stiffness and elastic properties of arterial walls in cholesterol-fed rabbits. Atherosclerosis 66: Howard, H.T.H., Nancy, C.C., Ossama, T. and Francis, S., Inductionof calcification in rabbit aortas by high cholesterol diets: roles of calcifiable vesicles in dystrophic calcification. Atherosclerosis. 161: Hudetz, A.G., Mark, G., Kovach, A.G.B., Kerenyi, T., Fody, L. and Monos, E., Biomechanical properties of normal and fibrosclerotic human cerebral arteries. Atherosclerosis. 39: Inkeles, S. and Eisenberg, D., Hyperlipidemia and coronary atherosclerosis: a review: Medicine (Baltimore) 60: Kissane, J.M., Anderson s Pathology (8th edition). CV Mosby Co: Miyazaki, A., Fukuda, K., Honda, M., Nishimoto, Y., Takahashi, M., Yamazaki, S., Shukuya, M., Masuda, Y. and Inagaki, 234 Saudi Journal of Biological Sciences Vol. 14, No (2) December, 2007

9 Effects of High Cholesterol and Saturated Fat Diet on the Aortic Wall Y., The study of the physical properties of the aortic wall in the white rabbit fed a high cholesterol diet. Proc Jpn Soc Biorheol (in Japanese) 6: P 251. Ooshima, A., Wakasaki, H., Bai, Y. and Muragaki, Y., Vascular constituents affecting arteriosclerosis with special emphasis on metabolic disorder of collagen. Exp Med (in Japanese) 6 : P Richter, H.A. and Mittermayer, C., Modulus of elasticity and compliance of normal and arteriosclerotic human aorta. Biorheology 12: Ross, R., The pathogenesis of atherosclerosis; a perspective for the 1990 s. Nature. 362: Rumiko, A., Hideo, I., Aki, N., Yoshinobu, I., Tsutomu, Y. and Junichiro, Y., Endothelial dysfunction precedes atherosclerotic lesions and platelet activation in high fat diet-induced prothrombotic state. Thrombosis Research. 117: Sandra L.P., Aortic thromboxane receptor deficiency alters vascular reactivity in cholesterol-fed rabbits. Atherosclerosis. 189: Sato, M. and Ohshima, N., Formation, development of arteriosclerosis and dynamic mechanical responses of the blood vessel wall. BME Jpn J Med Electr Biol Eng (in Japanese) 6: P 19. Shankar, R. and Bond, M.G., Correlation of noninvasive arterial compliance with anatomic pathology of atherosclerotic nonhuman primates. Atherosclerosis. 85: Stary, H.C., Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. Atherosclerosis. 9: Saudi Journal of Biological Sciences Vol. 14, No (2) December,

10 تأثريات الوجبة العالية من الكولسرتول والدهون املشبعة علي تركيب جدار أورطي األرانب النيوزيلندية البيضاء الذكور حممد أنور عبداحلليم - حممد سليمان العائد قسم الفيزياء والفلك - كلية العلوم - جامعة امللك سعود - اململكة العربية السعودية امللخص يستحوذ مرض تصلب الشرايني علي اهتمام كبري من الناحية الطبية مع زيادة أعداد األحباث األولية الكتشاف نشؤه وطرق تشخيصه وعالجه. أثناء تعاقب وتطور مرض تصلب الشرايني وعلي مدي واسع وبطرق عدة خمتلفة مت دراسة اخلواص امليكانيكية للجدار الشرياني يف عديد من احليوانات املغذاة علي وجبات غذائية غنية بالكولسرتول والدهون املشبعة وقد خلصت بعض النتائج البحثية إلي أن اجلدار الشرياني يصبح صلد أثناء تطور مرض تصلب الشرايني بينما أفادت بعض النتائج البحثية االخري العكس. ومن وجهة النظر التشخيصية والعالجية ملرض تصلب الشرايني تلعب التغريات البعدية واملورفولوجية يف اجلدار الشرياني أثناء تعاقب وتطور مرض تصلب الشرايني أدوار هامة. مع ذلك فالتغريات البعدية واملورفولوجية يف اجلدار الشرياني للحيوانات املغذاة علي وجبات عالية الكوليستريول والدهون املشبعة مل تدعم جيدا بالوثائق البحثية. من أجل ذلك الغرض فقد قمنا يف هذه الدراسة البحثية بتغذية جمموعة من األرانب علي وجبات غذائية عالية الكولسرتول بنسبة %5 مضافا إليها %5 من زيت الزيتون لفرتات تغذية ترتاوح بني أسبوع علي التعاقب وقد مت فحص تركيز الكولسرتول يف بالزما الدم والتغريات البعدية واملورفولوجية يف اجلدار الشرياني هلذه األرانب عقب كل فرتة من فرتات التغذية أثناء تطور مرض تصلب الشرايني. النتائج املستخلصة من هذه الدراسة البحثية هي زيادة تركيز الكوليستريول يف بالزما دم األرانب املغذاة علي وجبات عالية الكوليستريول والدهون املشبعة مع ميل يف زيادة مسك اجلدار الشرياني هلذه األرانب بطريقة إحصائية كافية خالل فرتات التغذية املتعاقبة. عالوة علي الزيادة اإلحصائية الكافية للنسبة بني مسك ونصف قطر العينات احللقية املأخوذة من اجلدار الشرياني للالرانب املغذاة علي وجبات عالية بالكولسرتول والدهون املشبعة مبقارنتها بالعينات احللقية املأخوذة من اجلدار الشرياني للالرانب املغذاة علي وجبات غذائية طبيعية وللتأكد من صحة هذه النتائج فقد قمنا بالفحص املورفولوجي لبعض من العينات احللقية املأخوذة من اجلدار الشرياني للالرانب املغذاة علي وجبات عالية الكولسرتول والدهون املشبعة وتلك املغذاة علي وجبات غذائية طبيعية وقد أظهر الفحص املورفولوجي الزيادة امللحوظة الواضحة يف طبقة الغشاء اخلارجية للجدار الشرياني هلذه األرانب وتكاثر العضالت امللساء وتكون األنسجة الضامة واخلاليا الدهنية احململة يف اجلزء السفلي من طبقة الغشاء اخلارجية. بينما أظهرت طبقة الغشاء الوسطي للجدار الشرياني متزق يف املرنني والكوالجني وخاليا العضالت امللساء والنقص املوضعي يف بناء طبقة الغشاء الوسطي للجدار الشرياني وقد لوحظ أيضا أن هذه النتائج كانت أكثر وضوحا يف شرايني األورطي الصدرية عن شرايني األورطي البطنية. 236 Saudi Journal of Biological Sciences Vol. 14, No (2) December, 2007