Effects of cell grafting on coronary remodeling after myocardial infarction

Jill J. Weyers, Stephen M. Schwartz, Elina Minami, Dara D. Carlson, Sarah K. Dupras, Kevin Weitz, Michael Simons, Timothy C. Cox, Charles E. Murry, William M. Mahoney

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

Background: With recent advances in therapeutic applications of stem cells, cell engraftment has become a promising therapy for replacing injured myocardium after infarction. The survival and function of injected cells, however, will depend on the efficient vascularization of the new tissue. Here we describe the arteriogenic remodeling of the coronary vessels that supports vascularization of engrafted tissue postmyocardial infarction (post-MI). Methods and Results: Following MI, murine hearts were injected with a skeletal myoblast cell line previously shown to develop into large grafts. Microcomputed tomography at 28 days postengraftment revealed the 3-dimensional structure of the newly formed conducting vessels. The grafts elicited both an angiogenic response and arteriogenic remodeling of the coronary arteries to perfuse the graft. The coronaries upstream of the graft also remodeled, showing an increase in branching, and a decrease in vascular density. Histological analysis revealed the presence of capillaries as well as larger vascular lumens within the graft. Some graft vessels were encoated by smooth muscle a-actin positive cells, implying that vascular remodeling occurs at both the conducting arterial and microvascular levels. Conclusions: Following MI and skeletal myoblast engraftment, the murine coronary vessels exhibit plasticity that enables both arteriogenic remodeling of the preexisting small branches of the coronary arteries and development of large and small smooth muscle encoated vessels within the graft. Understanding the molecular mechanisms underlying these 2 processes suggests mechanisms to enhance the therapeutic vascularization in patients with myocardial ischemia.

Original languageEnglish
Article numbere000202
JournalAmerican Heart Association. Journal. Cardiovascular and Cerebrovascular Disease
Volume2
Issue number3
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • Coronary angiography
  • Grafting
  • Myocardial infarction
  • Myocardial revascularization
  • Vascular remodeling

Cite this

Weyers, J. J., Schwartz, S. M., Minami, E., Carlson, D. D., Dupras, S. K., Weitz, K., ... Mahoney, W. M. (2013). Effects of cell grafting on coronary remodeling after myocardial infarction. American Heart Association. Journal. Cardiovascular and Cerebrovascular Disease, 2(3), [e000202]. https://doi.org/10.1161/JAHA.113.000202
Weyers, Jill J. ; Schwartz, Stephen M. ; Minami, Elina ; Carlson, Dara D. ; Dupras, Sarah K. ; Weitz, Kevin ; Simons, Michael ; Cox, Timothy C. ; Murry, Charles E. ; Mahoney, William M. / Effects of cell grafting on coronary remodeling after myocardial infarction. In: American Heart Association. Journal. Cardiovascular and Cerebrovascular Disease. 2013 ; Vol. 2, No. 3.
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title = "Effects of cell grafting on coronary remodeling after myocardial infarction",
abstract = "Background: With recent advances in therapeutic applications of stem cells, cell engraftment has become a promising therapy for replacing injured myocardium after infarction. The survival and function of injected cells, however, will depend on the efficient vascularization of the new tissue. Here we describe the arteriogenic remodeling of the coronary vessels that supports vascularization of engrafted tissue postmyocardial infarction (post-MI). Methods and Results: Following MI, murine hearts were injected with a skeletal myoblast cell line previously shown to develop into large grafts. Microcomputed tomography at 28 days postengraftment revealed the 3-dimensional structure of the newly formed conducting vessels. The grafts elicited both an angiogenic response and arteriogenic remodeling of the coronary arteries to perfuse the graft. The coronaries upstream of the graft also remodeled, showing an increase in branching, and a decrease in vascular density. Histological analysis revealed the presence of capillaries as well as larger vascular lumens within the graft. Some graft vessels were encoated by smooth muscle a-actin positive cells, implying that vascular remodeling occurs at both the conducting arterial and microvascular levels. Conclusions: Following MI and skeletal myoblast engraftment, the murine coronary vessels exhibit plasticity that enables both arteriogenic remodeling of the preexisting small branches of the coronary arteries and development of large and small smooth muscle encoated vessels within the graft. Understanding the molecular mechanisms underlying these 2 processes suggests mechanisms to enhance the therapeutic vascularization in patients with myocardial ischemia.",
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author = "Weyers, {Jill J.} and Schwartz, {Stephen M.} and Elina Minami and Carlson, {Dara D.} and Dupras, {Sarah K.} and Kevin Weitz and Michael Simons and Cox, {Timothy C.} and Murry, {Charles E.} and Mahoney, {William M.}",
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Weyers, JJ, Schwartz, SM, Minami, E, Carlson, DD, Dupras, SK, Weitz, K, Simons, M, Cox, TC, Murry, CE & Mahoney, WM 2013, 'Effects of cell grafting on coronary remodeling after myocardial infarction', American Heart Association. Journal. Cardiovascular and Cerebrovascular Disease, vol. 2, no. 3, e000202. https://doi.org/10.1161/JAHA.113.000202

Effects of cell grafting on coronary remodeling after myocardial infarction. / Weyers, Jill J.; Schwartz, Stephen M.; Minami, Elina; Carlson, Dara D.; Dupras, Sarah K.; Weitz, Kevin; Simons, Michael; Cox, Timothy C.; Murry, Charles E.; Mahoney, William M.

In: American Heart Association. Journal. Cardiovascular and Cerebrovascular Disease, Vol. 2, No. 3, e000202, 2013.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effects of cell grafting on coronary remodeling after myocardial infarction

AU - Weyers, Jill J.

AU - Schwartz, Stephen M.

AU - Minami, Elina

AU - Carlson, Dara D.

AU - Dupras, Sarah K.

AU - Weitz, Kevin

AU - Simons, Michael

AU - Cox, Timothy C.

AU - Murry, Charles E.

AU - Mahoney, William M.

PY - 2013

Y1 - 2013

N2 - Background: With recent advances in therapeutic applications of stem cells, cell engraftment has become a promising therapy for replacing injured myocardium after infarction. The survival and function of injected cells, however, will depend on the efficient vascularization of the new tissue. Here we describe the arteriogenic remodeling of the coronary vessels that supports vascularization of engrafted tissue postmyocardial infarction (post-MI). Methods and Results: Following MI, murine hearts were injected with a skeletal myoblast cell line previously shown to develop into large grafts. Microcomputed tomography at 28 days postengraftment revealed the 3-dimensional structure of the newly formed conducting vessels. The grafts elicited both an angiogenic response and arteriogenic remodeling of the coronary arteries to perfuse the graft. The coronaries upstream of the graft also remodeled, showing an increase in branching, and a decrease in vascular density. Histological analysis revealed the presence of capillaries as well as larger vascular lumens within the graft. Some graft vessels were encoated by smooth muscle a-actin positive cells, implying that vascular remodeling occurs at both the conducting arterial and microvascular levels. Conclusions: Following MI and skeletal myoblast engraftment, the murine coronary vessels exhibit plasticity that enables both arteriogenic remodeling of the preexisting small branches of the coronary arteries and development of large and small smooth muscle encoated vessels within the graft. Understanding the molecular mechanisms underlying these 2 processes suggests mechanisms to enhance the therapeutic vascularization in patients with myocardial ischemia.

AB - Background: With recent advances in therapeutic applications of stem cells, cell engraftment has become a promising therapy for replacing injured myocardium after infarction. The survival and function of injected cells, however, will depend on the efficient vascularization of the new tissue. Here we describe the arteriogenic remodeling of the coronary vessels that supports vascularization of engrafted tissue postmyocardial infarction (post-MI). Methods and Results: Following MI, murine hearts were injected with a skeletal myoblast cell line previously shown to develop into large grafts. Microcomputed tomography at 28 days postengraftment revealed the 3-dimensional structure of the newly formed conducting vessels. The grafts elicited both an angiogenic response and arteriogenic remodeling of the coronary arteries to perfuse the graft. The coronaries upstream of the graft also remodeled, showing an increase in branching, and a decrease in vascular density. Histological analysis revealed the presence of capillaries as well as larger vascular lumens within the graft. Some graft vessels were encoated by smooth muscle a-actin positive cells, implying that vascular remodeling occurs at both the conducting arterial and microvascular levels. Conclusions: Following MI and skeletal myoblast engraftment, the murine coronary vessels exhibit plasticity that enables both arteriogenic remodeling of the preexisting small branches of the coronary arteries and development of large and small smooth muscle encoated vessels within the graft. Understanding the molecular mechanisms underlying these 2 processes suggests mechanisms to enhance the therapeutic vascularization in patients with myocardial ischemia.

KW - Coronary angiography

KW - Grafting

KW - Myocardial infarction

KW - Myocardial revascularization

KW - Vascular remodeling

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U2 - 10.1161/JAHA.113.000202

DO - 10.1161/JAHA.113.000202

M3 - Article

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VL - 2

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