Translational Physiology: Porcine models of human coronary artery disease: implications for preclinical trials of therapeutic angiogenesis

2003 ◽  
Vol 94 (5) ◽  
pp. 1689-1701 ◽  
Author(s):  
G. Chad Hughes ◽  
Mark J. Post ◽  
Michael Simons ◽  
Brian H. Annex

“Therapeutic angiogenesis” describes an emerging field of cardiovascular medicine whereby new blood vessels are induced to grow to supply oxygen and nutrients to ischemic cardiac or skeletal muscle. Various methods of producing therapeutic angiogenesis have been employed, including mechanical means, gene therapy, and the use of growth factors, among others. The use of appropriate large-animal models is essential if these therapies are to be critically evaluated in a preclinical setting before their use in humans, yet little has been written comparing the various available models. Over the past decade, swine have been increasingly used in studies of chronic ischemia because of their numerous similarities to humans, including minimal preexisting coronary collaterals as well as similar coronary anatomy and physiology. Consequently, this review describes the most commonly used swine models of chronic myocardial ischemia with special attention to regional myocardial blood flow and function and critically evaluates the strengths and weaknesses of each model in terms of utility for preclinical trials of angiogenic therapies.

2015 ◽  
Vol 241 (1) ◽  
pp. e94
Author(s):  
M. Schmid ◽  
J. Marti-Jaun ◽  
M. Bühler ◽  
M. Herová ◽  
M. Hersberger

2021 ◽  
Vol 12 ◽  
Author(s):  
Abraham J. Matar ◽  
Rebecca L. Crepeau ◽  
Gerhard S. Mundinger ◽  
Curtis L. Cetrulo ◽  
Radbeh Torabi

Over the past twenty years, significant technical strides have been made in the area of vascularized composite tissue allotransplantation (VCA). As in solid organ transplantation, the allogeneic immune response remains a significant barrier to long-term VCA survival and function. Strategies to overcome acute and chronic rejection, minimize immunosuppression and prolong VCA survival have important clinical implications. Historically, large animals have provided a valuable model for testing the clinical translatability of immune modulating approaches in transplantation, including tolerance induction, co-stimulation blockade, cellular therapies, and ex vivo perfusion. Recently, significant advancements have been made in these arenas utilizing large animal VCA models. In this comprehensive review, we highlight recent immune strategies undertaken to improve VCA outcomes with a focus on relevant preclinical large animal models.


2018 ◽  
Vol 48 (5) ◽  
pp. e12911 ◽  
Author(s):  
Richard A. Brown ◽  
Gregory Y. H. Lip ◽  
Chetan Varma ◽  
Eduard Shantsila

1997 ◽  
Vol 3 (S2) ◽  
pp. 311-312
Author(s):  
D. G. Vince ◽  
R. Shekhar ◽  
R. M. Cothren ◽  
S. E. Nissen ◽  
E. M. Tuzcu ◽  
...  

Traditional methods for studying human coronary artery disease have significant limitations. Angiography allows evaluation only of the geometry of the remaining lumen; it cannot provide information on the structural or cellular composition of the arterial wall, which is essential to understand the processes involved in the progression of atherosclerosis. Intravascular ultrasound (IVUS) imaging is a new technology that permits tomographical visualization of a cross section through the vessel wall (Fig 1 A.) The development and refinement of IVUS has provided a powerful in vivo method to assess plaque morphology. Recent clinical studies have documented its sensitivity in detecting atherosclerosis, and it is increasingly employed to assist in selecting an appropriate therapeutic intervention. Perhaps more importantly, the potential of IVUS to quantify the structure and geometry of normal and atherosclerotic coronary arteries will allow one to characterize specific lesions and to differentiate the plaques that lead to various clinical syndromes. This study presents a three-dimensional (3D) reconstruction technique suitable for clinical use that accurately preserves 3D geometric information throughout the cardiac cycle without requiring mechanical IVUS catheter withdrawal aids.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Jong-Tar Kuo ◽  
Hsiao-En Tsai ◽  
Ching-Ting Lin ◽  
Chih-I Lee ◽  
Pei-Ling Lee ◽  
...  

Background. MicroRNA-10a (miR-10a) inhibits transcriptional factor GATA6 to repress inflammatory GATA6/VCAM-1 signaling, which is regulated by blood flow to affect endothelial function/dysfunction. This study aimed to identify the expression patterns of miR-10a/GATA6/VCAM-1 in vivo and study their implications in the pathophysiology of human coronary artery disease (CAD), i.e., atherosclerosis. Methods. Human atherosclerotic coronary arteries and nondiseased arteries were used to detect the expressions of miR-10a/GATA6/VCAM-1 in pathogenic vs. normal conditions. In addition, sera from CAD patients and healthy subjects were collected to detect the level of circulating miR-10a. Results. The comparison of human atherosclerotic coronary arteries with nondiseased arteries demonstrated that lower levels of endothelial miR-10a are related to human atherogenesis. Moreover, GATA6/VCAM-1 (a downstream target of miR-10a) was highly expressed in the endothelium, accompanied by the reduced levels of miR-10a during the development of human atherosclerosis. In addition, CAD patients had a significantly lower concentration of miR-10a in their serum compared to healthy subjects. Conclusions. Our findings suggest that low miR-10a and high GATA6/VCAM-1 in the cardiovascular endothelium correlates to the development of human atherosclerotic lesions, suggesting that miR-10a signaling has the potential to be developed as a biomarker for human atherosclerosis.


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