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.
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.
|Yabluchanskiy, Andriy; Ma, Yonggang; DeLeon-Pennell, Kristine Y et al. (2016) Myocardial Infarction Superimposed on Aging: MMP-9 Deletion Promotes M2 Macrophage Polarization. J Gerontol A Biol Sci Med Sci 71:475-83|
|Mottahedi, Mohammad; Han, Hai-Chao (2016) Artery buckling analysis using a two-layered wall model with collagen dispersion. J Mech Behav Biomed Mater 60:515-24|
|(2016) Effect of Axial Stretch on Lumen Collapse of Arteries. J Biomech Eng 138:|
|Xiao, Yangming; Liu, Qin; Han, Hai-Chao (2016) Buckling Reduces eNOS Production and Stimulates Extracellular Matrix Remodeling in Arteries in Organ Culture. Ann Biomed Eng 44:2840-50|
|Halaney, David L; Sanyal, Arnav; Nafissi, Navid A et al. (2016) The effect of trabeculae carneae on left ventricular diastolic compliance: improvement in compliance with trabecular cutting. J Biomech Eng :|
|Chesnutt, Jennifer K W; Han, Hai-Chao (2016) Computational simulation of platelet interactions in the initiation of stent thrombosis due to stent malapposition. Phys Biol 13:016001|
|Lindsey, Merry L; Zouein, Fouad A; Tian, Yuan et al. (2015) Osteopontin is proteolytically processed by matrix metalloproteinase 9. Can J Physiol Pharmacol 93:879-86|
|Voorhees, Andrew P; DeLeon-Pennell, Kristine Y; Ma, Yonggang et al. (2015) Building a better infarct: Modulation of collagen cross-linking to increase infarct stiffness and reduce left ventricular dilation post-myocardial infarction. J Mol Cell Cardiol 85:229-39|
|Qi, Nan; Gao, Hao; Ogden, Raymond W et al. (2015) Investigation of the optimal collagen fibre orientation in human iliac arteries. J Mech Behav Biomed Mater 52:108-19|
|Luetkemeyer, Callan M; James, Rhys H; Devarakonda, Siva Teja et al. (2015) Critical buckling pressure in mouse carotid arteries with altered elastic fibers. J Mech Behav Biomed Mater 46:69-82|
Showing the most recent 10 out of 42 publications