Media Of Thoracic Aorta Research Articles

Cisplatin treatment reduces contraction to angiotensin II by altering expression of angiotensin II receptors: a pilot study.

The renin angiotensin system is a key regulator of blood pressure homeostasis. Angiotensin type 1 (AT1R) and 2 receptors (AT2R) have been investigated as targets for cisplatin-induced acute kidney injury; however, their therapeutic potential remains inconclusive. This pilot study aimed to determined the effect that acute cisplatin treatment had on angiotensin II (AngII)-induced contraction in blood vessels and expression profiles of AT1R and AT2R in mouse arteries and kidneys. Male C57BL/6 mice at 18week of age (n = 8) were treated with vehicle or bolus dose of cisplatin (12.5mg/kg). Thoracic aorta (TA), adnominal aorta (AA), brachiocephalic arteries (BC), iliac arteries (IL) and kidneys were collected for isometric tension and immunohistochemistry analysis. Cisplatin treatment reduced IL contraction to AngII at all doses (p < 0.01, p < 0.001, p < 0.0001); however, AngII did not induce contraction in TA, AA or BC in either treatment group. Following cisplatin treatment, AT1R expression was significantly upregulated in the media of TA (p < 0.0001) and AA (p < 0.0001), and in the endothelium (p < 0.05) media (p < 0.0001) and adventitia (p < 0.01) of IL. Cisplatin treatment significantly reduced AT2R expression in the endothelium (p < 0.05) and media (p < 0.05) of TA. In renal tubules, both AT1R (p < 0.01) and AT2R (p < 0.05) were increased following cisplatin treatment. Herein, we report that cisplatin reduces AngII-mediated contraction in IL and may be explained by an absence of normal counterregulatory expression of AT1R and AT2R, indicating other factors are involved.

HSP60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation

Ectopic expression of HSP60 in vascular cells is known to activate auto-immune response that is critical to atherogenic initiation. However, the pathogenic relevance of the aberrant HSP60 upregulation in intracellular signaling pathways associated with atherogenic consequences in vascular cells remains unclear. The aim of the present study was to determine the role of endogenous HSP60 in atherogenic transformation of endothelial cells and macrophages. After generating primary evidence of oxidized low density lipoprotein (OxLDL) induced HSP60 upregulation in human umbilical vein endothelial cells (HUVEC), its physiological relevance in high fat high fructose (HFHF) induced early atherogenic remodelling was investigated in C57BL/6J mice. Prominent HSP60 expression was recorded in tunica intima and media of thoracic aorta that showed hypertrophy, lumen dilation, elastin fragmentation and collagen deposition. Further, HSP60 overexpression was found to be prerequisite for its surface localization and secretion in HUVEC. eNOS downregulation and MCP-1, VCAM-1 and ICAM-1 upregulation with subsequent macrophage accumulation provided compelling evidences on HFHF induced endothelial dysfunction and activation that were also observed in OxLDL treated- and HSP60 overexpressing-HUVEC. OxLDL induced concomitant reduction in NO production and monocyte adhesion were prevented by HSP60 knockdown, implying towards HSP60 mediated possible regulation of the said genes. OxLDL induced HSP60 upregulation and secretion was also recorded in THP-1 derived macrophages (TDMs). HSP60 knockdown in TDMs accounted for higher OxLDL accumulation that correlated with altered scavenger receptors (SR-A1, CD36 and SR-B1) expression further culminating in M1 polarization. Collectively, the results highlight HSP60 upregulation as a critical vascular alteration that exerts differential regulatory role in atherogenic transformation of endothelial cells and macrophages.

Comparative Histological and Immunohistochemical Study on The Effect of Curcumin and Atorvastatin in Induced Atherosclerosis in Aorta and Cardiac Muscle of Male Rabbits

Background: curcumin has many pharmacological effects including antioxidant, anti-inflammation, eliminating free radicals, anti-tumor, lipid regulation and anti-coagulation. Objectives: to compare the histological effects of curcumin and atorvastatin in experimental induced atherosclerosis in the rabbit’s aorta and heart. Subjects and Methodology: thoracic aorta sections were prepared and stained by Hx&E, orcein, Masson's trichrome and immuonohistochemical staning using CD34. Cardiac sections were prepared and stained by Hx&E, Masson's trichrome stain and immuonohistochemical staning using troponin T. Morphometrical study included, the thickness of both tunica intima and media of thoracic aorta , area % of the elastic fibers contents of both tunica intima and media in thorathic aorta, and the area %of the immune reaction of CD34 in thoracic aorta . Results: the atherosclerotic group showed a significant increase in the thickness of both tunicae intima& media when compared with the control group. There was a significant decrease in elastic fibers content and significant increase in the mean area % of the immune reaction of CD34 versus control. In atorvastatin treated group: there was a significant increase in comparison to control group, while there was a significant decrease in comparison to atherosclerotic group. There was significant decrease in elastic fibers content and significant increase in the mean area % of the immune reaction of CD34 in comparison to control group. In curcumin treated group: the thickness of both tunica intima and media showed a significant increase in comparison to control group. Conclusion: curcumin has potential role in treatment of atherosclerosis and myocardial infarction.

Comparative Histological and Immunohistochemical Study on The Effect of Curcumin and Atorvastatin in Induced Atherosclerosis in Aorta and Cardiac Muscle of Male Rabbits

Background: curcumin has many pharmacological effects including antioxidant, anti-inflammation, eliminating free radicals, anti-tumor, lipid regulation and anti-coagulation. Objectives: to compare the histological effects of curcumin and atorvastatin in experimental induced atherosclerosis in the rabbit’s aorta and heart. Subjects and Methodology: thoracic aorta sections were prepared and stained by Hx&E, orcein, Masson's trichrome and immuonohistochemical staning using CD34. Cardiac sections were prepared and stained by Hx&E, Masson's trichrome stain and immuonohistochemical staning using troponin T. Morphometrical study included, the thickness of both tunica intima and media of thoracic aorta , area % of the elastic fibers contents of both tunica intima and media in thorathic aorta, and the area %of the immune reaction of CD34 in thoracic aorta . Results: the atherosclerotic group showed a significant increase in the thickness of both tunicae intima& media when compared with the control group. There was a significant decrease in elastic fibers content and significant increase in the mean area % of the immune reaction of CD34 versus control. In atorvastatin treated group: there was a significant increase in comparison to control group, while there was a significant decrease in comparison to atherosclerotic group. There was significant decrease in elastic fibers content and significant increase in the mean area % of the immune reaction of CD34 in comparison to control group. In curcumin treated group: the thickness of both tunica intima and media showed a significant increase in comparison to control group. Conclusion: curcumin has potential role in treatment of atherosclerosis and myocardial infarction.

The Effect of miR-155 on the Regulation of Hyperplasia of Middle Membrane of Blood Vessel in Rat Hypertension Model

Vascular smooth muscle cell (VSMC) abnormal proliferation is related to hypertension. P27 can arrest cell cycle and its downregulation is associated with hypertension. miR-155 plays a regulatory role in VSMC proliferation, while its relationship with hypertension is still unclear. Bioinformatics analysis reveals a relationship between p27 mRNA and miR-155. The present study explores miR-155's role in p27 expression, VSMC proliferation and apoptosis, as well as in the pathogenesis of hypertension. Dual luciferase assay verified the relationship between miR-155 and p27. miR155, p27, α-SMA, and Ki-67 expressions in the thoracic aorta media of rat hypertension model were detected. VSMCs were cultured in vitro and grouped into, anti-miR-NC, anti-miR-155, pIRES2-blank, pIRES2-p27, and anti-miR-155 + pIRES2-p27 groups followed by analysis of cell cycle by flow cytometry and cell proliferation by EdU staining. Hypertension rats were randomly divided into antagomir-155 and antagomir-control. Caudal artery systolic and diastolic pressures were measured. miR-155 suppressed p27 expression. miR-155 and Ki-67 expressions were significantly enhanced, while p27 and α-SMA levels were reduced in the tunica media from hypertension rats compared with control. Downregulation of miR-155 and/or upregulation of p27 obviously declined cell proliferation and arrested cell cycle in G1 phase. Antagomir-155 injection significantly decreased systolic and diastolic pressures, elevated p27 and α-SMA expressions in media, and reduced the thickness of tunica media. miR-155 enhances VSMC proliferation via regulating p27. miR-155 enhancement was related to hypertension. miR-155 plays a therapeutic effect in hypertension.

Effect of Captopril and Melatonin on Fibrotic Rebuilding of the Aorta in 24 Hour Light-Induced Hypertension

Chronic continuous light exposure leads to melatonin deficiency along with complex neurohumoral activation resulting in hypertension development in rats. The aim of this study was to show, whether continuous light induces fibrotic rebuilding of the aorta and whether the treatment with melatonin or angiotensin converting enzyme inhibitor captopril can prevent these potential alterations. In a six-week experiment, 3-month-old Wistar rats were divided into 4 groups (ten per group): controls, rats exposed to continuous light, exposed to continuous light plus treated with captopril (100 mg/kg/24 h) and exposed to continuous light plus treated with melatonin (10 mg/kg/24 h). Systolic blood pressure (SBP) and collagen type I and III in the media of thoracic aorta were measured. Continuous light induced hypertension and fibrotic rebuilding of the aorta in terms of enhancement of collagen I and III concentration in the aortic media. Both captopril and melatonin prevented SBP rise and reduced collagen III concentration in the aorta. However, only melatonin reduced collagen I and the sum of collagen I and III in the aortic tissue. We conclude that in continuous light-induced hypertension, administration of melatonin, along with SBP reduction, decreases collagen I and III concentration in the aorta. It is suggested that antifibrotic effect of melatonin may reduce the stiffness of the aorta and small arteries and beneficially influence the nature of the pulse wave and peripheral vascular resistance.

Myosin isozymes in rabbit and human smooth muscles.

Although multiple forms of myosin in cardiac and skeletal muscles have been identified, it has not been firmly established that myosin isozymes are present in adult smooth muscle. Myosin, extracted from human thoracic aorta and lower saphenous vein and rabbit aorta and uterus, was analyzed by pyrophosphate gel electrophoresis to determine if myosin isozymes are present in these tissues. In all smooth muscle tissues studied, two myosin isozymes were detected and labelled as smooth muscle 1 and smooth muscle 2, smooth muscle 2 being the faster migrating isozyme. Bovine cultured smooth muscle cells from the media of thoracic aorta also contained two forms of myosin. However, cultured fibroblasts contained only one form of myosin. Extracting myosin from either relaxed or contracting rabbit aortic smooth muscle did not influence the mobilities of smooth muscle 1 and smooth muscle 2 on pyrophosphate gels, suggesting that the degree of light chain phosphorylation did not significantly alter the electrophoretic mobility under our conditions. Smooth muscle 1 and smooth muscle 2 myosins each contain heavy chains (200,000 daltons) and light chains (20,000 and 17,000 daltons) in addition to filamin (235,000 daltons), which is closely associated with the native protein. Myosin peptide maps of rabbit aorta and uterus revealed areas of substantially different banding patterns between smooth muscle 1 and smooth muscle 2 from the same tissue. Similar peptide maps of smooth muscle 1 bands were produced from the different tissues, but the smooth muscle 2 maps were dissimilar.(ABSTRACT TRUNCATED AT 250 WORDS)

慢性腎不全ラットの動脈硬化に関する検討

Accelerated arteriosclerosis is thought to be a major factor increasing morbidity and mortality in uremic patients. Since there is a lack of definite clinical evidence supporting this concept, the present experiments was undertaken to study the relations between uremia and arteriosclerosis using an experimental uremic model in male Wistar rats.Chronic uremia was induced by 5/6 resection of the total kidney. Six or eight months later, blood was obtained after overnight fasting and the thoracic aorta was removed, 6 components in media of thoracic aorta, namely, smooth muscle cell (SMC), eastin (EL), collagen (CL), acid mucopolysaccharides (AMPS), glycoprotein (GP), and calcium phosphate (Cal), were stained specifically and measured by the method of microspectrophotometry (MSP). Furthermore, biochemical studies were performed on these materials. The results obtained were as follows:1) By histochemical observation, abnormality of 6 components of media were found particularly in advanced uremic rats.2) Increase of SMC, and decrease of EL and AMPS were observed by MSP in uremic rats. There was no significant difference in CL and GP between uremic rats and controls.3) There was no significant difference in plasma calcium between uremic rats and controls. Plasma phosphorus was elevated in uremic rats. Aortic calcium and phosphorus contents were markedly elevated, particularly in advanced uremic rats.

Diffusional support of arteries.

The relative role of the arterial lumen, adventitial vasa vasorum, and medial vasa vasorum in nutritional support of arteries is unclear. We have used a newly developed autoradiographic method to study diffusion of metabolically inert [14C]antipyrine into arteries to determine the relative importance of different pathways in nutritional support of arteries. [14C]antipyrine was homogenously distributed across the media of small arteries within 15 s, which indicates that diffusion into the central media was rapid. In the thoracic and abdominal aorta, levels of antipyrine were higher in the inner media (P less than 0.05) than in the middle of the media. Levels of antipyrine in outer media of the thoracic aorta (which has medial and adventitial vasa) were comparable to those observed in the inner media, but antipyrine levels were lower in outer than in inner media of the abdominal aorta (which has adventitial vasa only). Ligation of intercostal arteries, which are the source of medial vasa vasorum in the thoracic aorta, decreased diffusional support to the outer media of the thoracic aorta. We conclude that 1) diffusional support is more effective in thinner muscular arteries than in the aorta, 2) both luminal and abluminal sources of nutrition are important, particularly for the aorta, 3) vasa vasorum appear to be important for adequate diffusional support of the thoracic aortic media, and 4) medial vasa vasorum may be more effective than adventitial vasa vasorum in nourishing the aorta.

動脈硬化家兎大動脈の機能と構築障害

Antisclerotic effect of clinofibrate (lipoclin®) was studied referring to rise and fall of aortic pulse wave velocity (PWV) and observation of aortic wall constituents of rabbits with experimental arteriosclerosis.Twenty-seven male rabbits of 38 months were divided into the healthy group (H group) of 13 rabbits, the sclerotic group (S group) of 9, and the clinofibrate (200mg/day) administration group (A group) of 5 respectively. Arteriosclerosis was produced by contaminant use of three method, namely, hypoxic method (N2 gas inhalation), tissue injury method (intramuscular injection of norepinephrine) and intimal lesion formation and vaso vasorum obstruction (administration of 0.5g cholesterol) for S and A group. PWV and blood pressure measured every two weeks to see their rise and fall. After 16 weeks all the rabbits were killed and 6 components in media of thoracic aorta, namely, smooth muscle cell (SMC), elastin (EL), collagen (CL), acid mucopolysaccharides (AMPS), glycoprotein (GP) and calcium phosphate (Ca) were observed and assayed histochemically by microspectrophotometric procedure. Furthermore, a principal component analysis was conducted to generally evaluate differences among those 3 groups as to changes of those 5 components.When changes of PWV (ΔPWV) on an average of 4 weeks were studied, no change was observed in the H group, but in the S group, it increased about 1.0m/sec after the 10th week in S group and it decreased about 1.0m/sec after 4 weeks in the A group. Upon comparison between the S and A groups, after 4 weeks with the level of significance at 1%, a significant difference was noted, the effect of which lasted until the 16th week.Upon histochemical observation, atrophy, disappearance and decrease of SMC, fragmentation and disappearance of EL and CL, uneven distribution and increase of AMPS and GP, and increase of calcium phosphate were noted in the S group, while in the A group either component received only mild disturbances. Amount of the components with the H group, S group and A group respectively were as follows: SMC: 40.6±6.6, 32.6±4.4, 35.7±4.7%E, EL: 52.8±4.3, 42.3±2.6, 46.3±4.3%E, Cl: 38.3±4.0, 33.3±3.7, 39.0±3.3%E, AMPS: 28.4±6.6, 35.7±5.4, 34.2±3.4%E, GP: 33.2±3.7, 39.7±3.7, 36.9±3.5%E. Upon principal component analysis and a study of their distribution on the quadratic coordinates in comparison of those 3 groups, it was suggested that distribution of the A group being near the region of the H group. It was suggested that clinofibrate inhibits a organic arteriosclerotic lesion.

動脈硬化家兎の機能と構築障害

Effect of soysterol obtained from soybeans was studied referring to rise and fall of aortic pulse wave velocity (PWV) of rabbits with experimental arteriosclerosis, observation of arterial wall constituents and assay.Twenty-seven male rabbits of 38 months were divided into the healthy group (H group) of 13 rabbits, the sclerotic group (S group) of 9, and the soysterol administration group (A group) of 5 respectively. For producing arteriosclerosis, N2 gas inhalation, intramuscular injection of norepinephrin and oral administration of cholesterol were used combinedly. To the A group at the same time as loading 200 mg of soysterol (Moristerol®) was given once a day. PWV and blood pressure were measured every two weeks to see their rise and fall. After 22 weeks all the rabbits were killed and 6 components in media of thoracic aorta, namely, smooth muscle cell (SMC), nuclear DNA (DNA), elastin (EL), collagen (CL), acid mucopolysaccharides (AMPS), and glycoprotein (GP) were observed histochemically by MSP and assayed. Furthermore, a series of principal component analysis was conducted to generally evaluate differences among those 3 groups as to changes of those 6 components. When rise and fall of PWV in those 3 groups were observed with average regression coefficient, it was 0.0109 m/sec/W with the H group, 0.0626 m/sec/W with the S group and-0.0326 m/sec/W with the A group, showing the lower value with the A group than that of the S group. An average PWV changes (ΔPWV) in every 3 months was hardly observed in the H group, but in the S group after 6 weeks, it increased by 0.9 m/sec on an average. On the other hand in the A group during the total course, an apparent decreasing trend was observed, and a significant decrease was noted 6 weeks after starting of administration onward. Upon histochemical observation, atrophy, disappearance and decrease of SMC, fragmentation and disappearance of EL and CL, uneven distribution and increase of AMPS and GP, and increase of calcium phosphate were noted in the S group, while in the A group either component received only mild disturbances, showing intermediary values between H group and S group. Amount of the components with the H group, S group and A group respectively were as followsSMC: 40.6±6.6, 32.6±4.4, 40.6±8.0% EDNA: 293.8±61.8, 283.1±51.2, 316.0±74.9% EEL: 52.8±4.3, 42.3±2.6, 51.6±7.5% ECL: 38.8±4.0, 33.3±3.7, 37.3±1.8% EAMPS: 28.4±6.6, 35.7±5.4, 32.7±2.7% EGP: 33.2±3.7, 39.7±5.3, 36.1±3.8% EUpon principal component analysis and a study of their distribution on the quadratic coordinates in comparison of those 3 groups, it was suggested that distribution of the A group being near the region of the H group, soysterol has an antiarteriosclerotic effect.