Biomechanical Mechanisms of Artery Tortuosity

动脉迂曲的生物力学机制

• 批准号: 8208052
• 负责人: HAI-CHAO HAN
• 金额: $ 35.85万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8208052
• 关键词: Address; Affect; Aging; Aging-Related Process; Aneurysm; Aorta; Arterial Fatty Streak; Arteries; Atherosclerosis; Behavior; Biological; Biological Models; Biomechanics; Biomedical Engineering; Blood Pressure; Blood Vessels; Blood capillaries; Blood flow; Carotid Arteries; Cell Proliferation; Cell physiology; Cerebrum; Clinical; Clinical Research; Collagen; Computer Simulation; Coronary; Coronary artery; Development; Disease; Elastases; Elastic Fiber; Elastin; Endothelium; Environment; Etiology; Event; Experimental Models; Extracellular Matrix; Family suidae; Finite Element Analysis; Foundations; Future; Gelatinase A; Gene Mutation; Genetic; Goals; Human; Hypertension; Knowledge; Lead; Link; Liquid substance; Loeys-Dietz Syndrome; Longitudinal Studies; Matrix Metalloproteinases; Measures; Mechanical Stress; Mechanics; Medical Research; Methods; Minor; Modeling; Organ Culture Techniques; Outcome; Patients; Pattern; Peripheral Vascular Diseases; Peripheral arterial disease; Physiological; Play; Predisposition; Prevention; Production; Property; Pulsatile Flow; Reporting; Research; Research Project Grants; Role; Rupture; Smooth Muscle Myocytes; Spatial Distribution; Staging; Straight Artery of the Endometrium; Stress; Structure; Symptoms; Syndrome; System; Techniques; Testing; Theoretical model; Thrombosis; Time; Validation; Variant; Vascular Diseases; Vertigo; Work; arteriole; base; biomechanical engineering; capillary; collagenase; design; femoral artery; fibulin; hemodynamics; high risk; iliac artery; in vivo; innovation; interest; mathematical model; novel; pressure; prevent; public health relevance; research study; response; shear stress; simulation; spatiotemporal; tissue regeneration; tool

DESCRIPTION (provided by applicant): This is a resubmission of an application in response to PA-07-279 Bioengineering Research Grant (R01), which supports basic and applied multi-disciplinary research that addresses important biological, bioengineering or medical research problems using an integrative, systems approach. Targeted Problem: Artery tortuosity occurs when normally straight arteries take an abnormal curved and tortuous path. Tortuous arteries are common angiographic findings in humans and occur in a multitude of arteries, from aorta to capillary, cerebral to coronary arteries, and carotid to femoral arteries. Tortuous "corkscrew" collateral arteries frequently occur in patients with occlusive peripheral vascular disease. Clinical studies suggest that high blood pressure, aging, atherosclerosis, and rare genetic mutations are each associated with higher risks of artery tortuosity, and tortuosity is believed to precipitate the development of atherosclerosis and hypertension. However, the underlying etiology and biomechanical mechanism of artery tortuosity remain unclear. The objective of this study is to determine the biomechanical mechanisms of artery tortuosity by investigating the interactions between vascular hemodynamics, buckling, and wall remodeling. Our central hypothesis is that elevated pulsatile pressure or weakened arterial wall initiates arterial buckling which then stimulates asymmetric wall remodeling that exacerbate buckling and gradually leads to arterial tortuosity. The two specific aims are to determine what types of blood flow, mechanical stress, and wall property changes initiate artery buckling and how buckling affects arterial blood flow and wall stress, as well as the associated adaptation of the arterial wall that leads to tortuosity. Methods: Artery buckling will be examined using biomechanics-based modeling and experimental tests under pulsatile flow conditions. The effect of wall matrix degradation on artery buckling will be evaluated in porcine carotid arteries using elastase and collagenase treatments to degrade specific matrix components. The blood flow, wall stress, and arterial wall remodeling in buckled arteries will be examined using a unique ex vivo organ culture system combined with computational modeling. Outcomes: This study will establish mathematical and experimental models of artery dynamic buckling to determine the mechanisms that define the relationship among mechanical stress, artery buckling, and wall remodeling. Benefits: The new knowledge obtained from these studies will provide guidance in developing new techniques for the prevention and treatment artery tortuosity by targeting the mechanical factors and broaden our knowledge of vascular biomechanics. PUBLIC HEALTH RELEVANCE: Artery tortuosity occurs when the normally straight arteries take a tortuous path, which impairs normal blood flow causes many symptoms. Tortuosity is often associated with hypertension, aging, and atherosclerosis. Tortuous "corkscrew" collateral arteries are common in patients with peripheral artery disease. Mechanical factors play a significant role in artery tortuosity. Understanding the biomechanical mechanisms how tortuosity initiates and develop will reveal its role in vascular disease and lead to new understanding of vascular disease and set a basis for development of new treatment.

描述（由申请人提供）：这是对PA-07-279生物工程研究资助（R 01）的申请的重新提交，该资助支持基础和应用多学科研究，使用综合系统方法解决重要的生物学，生物工程或医学研究问题。 目标问题：当正常的直动脉采取异常弯曲和曲折的路径时，就会发生动脉迂曲。动脉迂曲是人类常见的血管造影结果，并且发生在许多动脉中，从主动脉到毛细血管，从脑动脉到冠状动脉，以及颈动脉到股动脉。闭塞性周围血管疾病患者的侧支动脉常呈螺旋状弯曲。临床研究表明，高血压、衰老、动脉粥样硬化和罕见的基因突变都与动脉迂曲的高风险相关，而迂曲被认为会加速动脉粥样硬化和高血压的发展。然而，动脉迂曲的潜在病因和生物力学机制仍不清楚。本研究的目的是通过研究血管血流动力学、屈曲和血管壁重塑之间的相互作用来确定动脉迂曲的生物力学机制。我们的中心假设是，脉动压力升高或动脉壁变弱引发动脉屈曲，然后刺激不对称的壁重塑，加剧屈曲并逐渐导致动脉迂曲。这两个具体目标是确定什么类型的血流、机械应力和壁特性变化引发动脉屈曲，以及屈曲如何影响动脉血流和壁应力，以及导致迂曲的动脉壁的相关适应。方法：动脉屈曲将使用生物力学为基础的建模和实验测试脉动流条件下进行检查。将在猪颈动脉中使用弹性蛋白酶和胶原酶处理降解特定基质组分，评价壁基质降解对动脉屈曲的影响。将使用独特的离体器官培养系统结合计算建模来检查屈曲动脉中的血流、壁应力和动脉壁重塑。成果：本研究将建立动脉动态屈曲的数学和实验模型，以确定机械应力、动脉屈曲和壁重塑之间关系的机制。优点：从这些研究中获得的新知识将为开发针对力学因素的预防和治疗动脉迂曲的新技术提供指导，并拓宽我们对血管生物力学的认识。 公共卫生关系： 动脉迂曲发生在正常的直动脉采取曲折的路径，这损害了正常的血流导致许多症状。迂曲通常与高血压、衰老和动脉粥样硬化有关。迂曲的“螺旋形”侧支动脉在外周动脉疾病患者中很常见。机械因素在动脉迂曲中起重要作用。了解迂曲发生和发展的生物力学机制将揭示其在血管疾病中的作用，并导致对血管疾病的新认识，为开发新的治疗方法奠定基础。