Aging and atherosclerosis in the rabbit

Spagnoli, Luigi Giusto; Orlandi, Augusto; Mauriello, Alessandro; Santeusanio, Giuseppe; Angelis, Clara De; Lucreziotti, Rita; Ramacci, M. T.

doi:10.1016/0021-9150(91)90003-l

Cited by 91 publications

(28 citation statements)

References 34 publications

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“…However, it is possible that the microenvironment surrounding cells influences the cell behavior. For example, we previously reported that the migration of aged AoSMCs on a gelatin rich matrix was different due to differences in metalloproteinase 2 activity (20). The absence of an external matrix in the model used in the experiments described in this report highlights the specific role of HA in AoSMC migration.…”

Section: Discussionmentioning

confidence: 68%

“…There is a clear correlation between aging and the probability for onset of cardiovascular diseases (20). For this reason, we studied HA metabolism in AoSMCs during in vitro aging to verify whether they could modify their matrix environment with aging and acquire a more susceptible phenotype that could promote vascular diseases.…”

Section: Discussionmentioning

confidence: 99%

“…As aging is one of the major risk factors for the insurgence of vascular pathology (20), we have established a cell model for in vitro aging in order to investigate age related modifications in gene expression and cellular migration in primary human aortic SMCs (AoSMCs). Recently, we used this aging model to describe age related changes in expression and activity of matrix metalloproteinase 2 (21).…”

Section: Hyaluronan (Ha)mentioning

confidence: 99%

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Hyaluronan-CD44-ERK1/2 Regulate Human Aortic Smooth Muscle Cell Motility during Aging

Vigetti

Viola

Karousou

et al. 2008

Journal of Biological Chemistry

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The glycosaminoglycan hyaluronan (HA) modulates cell proliferation and migration, and it is involved in several human vascular pathologies including atherosclerosis and vascular restenosis. During intima layer thickening, HA increases dramatically in the neointima extracellular matrix. Aging is one of the major risk factors for the insurgence of vascular diseases, in which smooth muscle cells (SMCs) play a role by determining neointima formation through their migration and proliferation. Therefore, we established an in vitro aging model consisting of sequential passages of human aortic smooth muscle cells (AoSMCs). Comparing young and aged cells, we found that, during the aging process in vitro, HA synthesis significantly increases, as do HA synthetic enzymes (i.e. HAS2 and HAS3), the precursor synthetic enzyme (UDP-glucose dehydrogenase), and the HA receptor CD44. In aged cells, we also observed increased CD44 signaling that consisted of higher levels of phosphorylated MAP kinase ERK1/2. Further, aged AoSMCs migrated faster than young cells, and such migration could be modulated by HA, which alters the ERK1/2 phosphorylation. HA oligosaccharides of 6.8 kDa and an anti-CD44 blocking antibody prevented ERK1/2 phosphorylation and inhibited AoSMCs migration. These results indicate that, during aging, HA can modulate cell migration involving CD44-mediated signaling through ERK1/2. These data suggest that age-related HA accumulation could promote SMC migration and intima thickening during vascular neointima formation. Hyaluronan (HA)2 is a linear, unsulfated glycosaminoglycan (GAG) that is composed of repeating units of D-glucuronic acid and N-acetylglucosamine linked together through alternating ␤1,4 and ␤1,3 glycosidic bonds. The amount and the molecular weight of HA are important factors that regulate the physiopathological effects that this molecule displays on cells (1). In mammals, three specific HA synthases (HAS1, -2, and -3) and three hyaluronidases (HYAL1, 2, and PH20) regulate HA synthesis and degradation with specific biochemical properties and distributions in adult as well as in embryonic tissues (2, 3). Therefore, these enzymes have a critical role in HA metabolism and are responsible for HA balance in the extracellular matrix (ECM).Hydrated HA makes the ECM an ideal environment in which cells can move and proliferate. Moreover, HA is an important space filling molecule as is evident in the vitreous humor, the dermis and the synovial fluid of joints. Besides its chemical and mechanical properties, HA interacts with several receptors at the cellular level that specifically trigger various signal transduction responses (4). The HA receptor CD44 is expressed on the surface of most cells, including immune system cells, and it mediates cell adhesion, proliferation and migration (5). Receptor for HA-mediated motility (RHAMM) mediates cellular motility (6). Lyve-1 is the specific HA receptor of the lymphatic system although very recent evidences indicate a more complex function of this protein unrelated to HA...

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Hyaluronan (Ha)mentioning

confidence: 99%

See 1 more Smart Citation

Hyaluronan-CD44-ERK1/2 Regulate Human Aortic Smooth Muscle Cell Motility during Aging

Vigetti

Viola

Karousou

et al. 2008

Journal of Biological Chemistry

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“…Aortic lipid deposits in people and cholesterol-fed rabbits have an age-related distribution and composition (Spagnoli et al 1991;Barnes & Weinberg 1998, 1999, 2001Orlandi et al 2000). In immature rabbit and human aortas, lesions develop at the downstream margin of intercostal branch ostia and are restricted to fatty streaks, whereas in mature aortas of both species lesions occur at the sides and upstream of the branch ostia and have a more complex, fibrous composition ( Weinberg 2002).…”

Section: Introductionmentioning

confidence: 99%

Application of Fourier transform infrared spectroscopic imaging to the study of effects of age and dietary l -arginine on aortic lesion composition in cholesterol-fed rabbits

Palombo

Cremers

Weinberg

et al. 2008

J. R. Soc. Interface.

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Diet-induced atherosclerotic lesions in the descending thoracic segment of rabbit aorta were analysed ex vivo by micro-attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopic imaging. The distribution and chemical character of lipid deposits within the arterial wall near intercostal branch ostia were assessed in histological sections from immature and mature rabbits fed cholesterol with or without L-arginine supplements. Previous studies have shown that both these properties change with age in cholesterol-fed rabbits, putatively owing to changes in the synthesis of nitric oxide (NO) from L-arginine. Immature animals developed lesions at the downstream margin of the branch ostium, whereas lipid deposition was observed at the lateral margins in mature animals. Dietary L-arginine supplements had beneficial effects in mature rabbit aorta, with overall disappearance of the plaques; on the other hand, they caused only a slight decrease of the lipid load in lesions at the downstream margin of the ostium in immature rabbits. ATR-FTIR imaging enabled differences in the lipid to protein density ratio of atherosclerotic lesions caused by age and diet to be visualized. Lipid deposits in immature rabbits showed higher relative absorbance values of their characteristic spectral bands compared with those in immature L-arginine-fed rabbits and mature rabbits. The multivariate methods of principal component analysis (PCA) and factor analysis (FA) were employed, and relevant chemical and structural information were obtained. Two distinct protein constituents of the intima-media layer at different locations of the wall were identified using the method of FA. This approach provides a valuable means of investigating the structure and chemistry of complex heterogeneous systems. It has potential for in vivo diagnosis of pathology.

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“…Cholesterol-fed rabbits are widely used for research on atherosclerosis [5-7, 12, 20], fat metabolism [2,4,7], and vascular remodeling [11,29,30,32] et cetera. Previous structural studies in cholesterol-fed rabbits observed high-grade vascular occlusive lesions in the coronary artery [4,20,22,25] and aorta [2,6,12,16,22,25,31,36], but little is known about the pathosis of the lung. Incidentally, perfusion pressure of the lung is lower, as is that of the heart, than that of the aorta.…”

mentioning

confidence: 99%

Pulmonary Atherosclerosis and Pulmonary Arterial Pressure in Cholesterol-Fed New Zealand White Rabbits.

Kamimura

Suzuki

Miura

et al. 2001

The Journal of Veterinary Medical Science

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ABSTRACT. The lung produces many vasoactive substances originating from its vascular endothelium and plays an important part in various pathose. The present study was carried out to clarify pulmonary atherosclerosis and pulmonary arterial pressure, and to elucidate a part of the pulmonary pathosis in cholesterol-fed rabbits. Atherosclerosis was induced by feeding the animals a cholesterol-rich diet. When the rabbits were fed the cholesterol-enriched diets for 15 weeks, the grade of the atherosclerosis was severer than in 8W-feeding rabbits. The lesions of 8W-feeding rabbits were mainly composed of foam cells and fibrous components, whereas in 15W-feeding rabbits, the aggregation of foam cells beneath the endothelium of the vessel was infiltrating the media and severe stenose of the lumen was observed. In the entire pulmonary arterial system, the severe obstructive vascular lesions were localized and not diffused. The pulmonary arterial pressures of the rabbits increased slightly with time and the mean pressures were 11.3 ± 0.9 (control group), 11.8 ± 1.0 (8W group) and 13.7 ± 1.5 mmHg (15W group) respectively. A significant difference existed in the mean pressure between the control group and 15W-feeding group, but there were no significant differences in the systolic and diastolic pressures among the three groups. In conclusion, we could induce pulmonary atherosclerosis in rabbits by feeding them a hyper-cholesterol diet but not overt pulmonary hypertension. KEY WORDS: cholesterol-fed rabbit, pulmonary atherosclerosis, pulmonary hypertension. J. Vet. Med. Sci. 63(6): 647-653, 2001The lung produces many vasoactive substances, such as endothelin [9,24], nitric oxide [3,15,19] and adrenomedullin [21,35], that originate in the vascular endothelial cells and has receptors [17,26]. So it is thought that the lung plays an important role in hemodynamic regulation and in various pathose. Many researchers are performing investigations on the lung of refractory diseases such as primary pulmonary hypertension. Cholesterol-fed rabbits are widely used for research on atherosclerosis [5-7, 12, 20], fat metabolism [2,4,7], and vascular remodeling [11,29,30, 32] et cetera. Previous structural studies in cholesterol-fed rabbits observed high-grade vascular occlusive lesions in the coronary artery [4,20,22,25] and aorta [2,6,12,16,22,25,31,36], but little is known about the pathosis of the lung. Incidentally, perfusion pressure of the lung is lower, as is that of the heart, than that of the aorta. Based on the above observation, we hypothesized that pulmonary atherosclerosis and vascular obstructive lesion-induced pulmonary hypertensive-state could be observed in cholesterol-fed rabbits. This study was conducted to clarify the progression of pulmonary atherosclerosis and the pulmonary arterial pressure in cholesterol-fed rabbits and to investigate whether the rabbits would be suitable as a pulmonary hypertension model animal or not.

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Aging and atherosclerosis in the rabbit

Cited by 91 publications

References 34 publications

Hyaluronan-CD44-ERK1/2 Regulate Human Aortic Smooth Muscle Cell Motility during Aging

Hyaluronan-CD44-ERK1/2 Regulate Human Aortic Smooth Muscle Cell Motility during Aging

Application of Fourier transform infrared spectroscopic imaging to the study of effects of age and dietary l -arginine on aortic lesion composition in cholesterol-fed rabbits

Pulmonary Atherosclerosis and Pulmonary Arterial Pressure in Cholesterol-Fed New Zealand White Rabbits.

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