BIOENGINEERING-BIOLOGICAL STUDY OF ARTERIAL DISEASE

动脉疾病的生物工程生物学研究

• 批准号: 3348006
• 负责人: HARVEY S. BOROVETZ
• 金额: $ 16.65万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1991-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3348006
• 关键词: actins; artery occlusion; atherosclerosis; blood lipoprotein transport; carotid artery; catalase; cholesterol; cholesterol esters; dogs; fluorescence microscopy; hemodynamics; laboratory rabbit; lysophospholipase; mathematical model; model design /development; myosins; perfusion; radiotracer; scanning electron microscopy; tissue /cell culture

The aim of the proposed renewal project is to further our understanding of the role of hemodynamics in atherogenesis; in particular to elucidate mechanisms by which hemodynam ic/biomechanical forces modulate the transcytotic and cellular responses of the vessel wall. A multidisciplinary research team has joined forces in an integrated approach to accomplish our stated aims. Our research plan is built around a novel and reliable in vitro pulsatile perfusion apparatus which exposes freshly excised animal and human vessels (arteries and veins) to well-defined hemodynamics. An important feature of this device is that hemodynamic parameters (e.g., intraluminal pressure, transmural pressure, pulse pressure, rate of flow, etc.) can be individually varied and the biologic/biomechanical response of the vessel wall studied in detail. It is our hypothesis that the de- livery of defined, realistic hemodynamics in vitro provides an environment in which we are able to study, on a fundamental level, how hemodynamic forces influence molecular and cellular aspects of the disease process. Specific timely questions that our studies will address include: i) why vein grafts may "fail" when sewn into the arterial circulation; in particular which arterial hemodynamic parameter(s) modulate the normal metabolic and cellular response of veins; ii) how cellular metabolism, structure and function are influenced by "high" versus "low" shear stress; iii) whether cytoskeletal adaptation to hemodynamic/biomechanical forces contributes to the characteristicallyfocal nature of atherogenesis in vivo; iv) if hemodynamics initiate extracellular matrix reorganization by altering arterial wall metabolism; v) if hemodynamics (e.g., hypertension) accererates lipid accumulation and cellular metabolism at or adjacent to sites of plaque versus lesion free areas; vi) which cell types are most active in LDL degradation in atherosclerotic and non-atherosclerotic portions of human arteries perfused in vitro and which receptors, if any, are involved in this cellular uptake; and, vii) whether "disease susceptible" versus "disease resistant" arteries differ as a function of the aforementioned parameters in response to hemodynamics. To our best knowledge, this integrated approach in which we systematically vary individual hemodynamic parameters and measure the biologic response of the vessel wall to these hemodynamic variables, is unavailable in other bioengineering protocols and marks s important advance toward understanding the role of hemodynamics an atherogenesis.

拟议的重建项目的目的是促进我们的

项目成果

Measurement in vitro of pulsatile arterial diameter using a helium-neon laser.

使用氦氖激光器体外测量脉动动脉直径。

• DOI: 10.1152/jappl.1987.62.2.679
• 发表时间: 1987
• 期刊: Journal of applied physiology (Bethesda, Md. : 1985)
• 作者: Brant,AM;Rodgers,GJ;Borovetz,HS
• 通讯作者: Borovetz,HS

Evaluation of endothelium-derived nitric oxide mediated vasodilation utilizing ex vivo perfusion of an intact vessel.

利用完整血管的离体灌注评估内皮衍生的一氧化氮介导的血管舒张。

• DOI: 10.1016/0022-4804(92)90305-j
• 发表时间: 1992
• 期刊: The Journal of surgical research
• 作者: LigushJr,J;Labadie,RF;Berceli,SA;Ochoa,JB;Borovetz,HS
• 通讯作者: Borovetz,HS

Hemodynamics and low density lipoprotein metabolism. Rates of low density lipoprotein incorporation and degradation along medial and lateral walls of the rabbit aorto-iliac bifurcation.

• DOI: 10.1161/01.atv.10.5.686
• 发表时间: 1990-09
• 期刊: Arteriosclerosis
• 作者: S. Berceli;V. Warty;R. Sheppeck;W. A. Mandarino;S K Tanksale;H. Borovetz

Experimental determination and mathematical model of the transient incorporation of cholesterol in the arterial wall.

动脉壁中胆固醇瞬时掺入的实验测定和数学模型。

• DOI: 10.1007/bf02460805
• 发表时间: 1990
• 期刊: Bulletin of mathematical biology
• 影响因子: 3.5
• 作者: Neumann,SJ;Berceli,SA;Sevick,EM;Lincoff,AM;Warty,VS;Brant,AM;Herman,IM;Borovetz,HS
• 通讯作者: Borovetz,HS

Experimental determination of wall shear rate in canine carotid arteries perfused in vitro.

体外灌注犬颈动脉壁剪切率的实验测定。

• DOI: 10.1016/0021-9290(89)90216-9
• 发表时间: 1989
• 期刊: Journal of biomechanics
• 影响因子: 2.4
• 作者: Johnson,GA;Hung,TK;Brant,AM;Borovetz,HS
• 通讯作者: Borovetz,HS