Selective Matrix Metalloproteinase Inhibition Reduces Left Ventricular Remodeling but Does Not Inhibit Angiogenesis After Myocardial Infarction

Lindsey, Merry L.; Gannon, Joseph; Aikawa, Masanori; Schoen, Frederick J.; Rabkin, Elena; Lopresti‐Morrow, Lori; Crawford, Jamie; Black, Shawn C.; Libby, Peter; Mitchell, Peter G.; Lee, Richard T.

doi:10.1161/hc0602.103674

Cited by 178 publications

(136 citation statements)

References 37 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…This has indeed been borne out with basic proof of concept studies (20), particularly with the inhibition of MMP-9, one of the major gelatinases involved in postinfarct remodelling (21,22). Most of these studies demonstrate a reduction in ventricular size and improvement in ventricular function with administration of the MMP inhibitors (23)(24)(25).…”

Section: Mmps In Cardiovascular Diseasementioning

confidence: 99%

Matrix metalloproteinases in cardiovascular disease

Liu¹,

Sun²,

Sader³

2006

Canadian Journal of Cardiology

155

120

View full text Add to dashboard Cite

Section: Mmps In Cardiovascular Diseasementioning

confidence: 99%

Matrix metalloproteinases in cardiovascular disease

Liu¹,

Sun²,

Sader³

2006

Canadian Journal of Cardiology

155

120

View full text Add to dashboard Cite

“…MMPs are regulated at multiple levels, including transcription, translation, secretion, and activation. 17 Plasmin, TGFß1, TNFa, and IL-1ß are some examples for the mediators that are involved in the MMP regulation; 16 however, it remains unclear which are secreted by the stem cells and how the beneficial effects are induced.…”

mentioning

confidence: 99%

Effects of Autologous Stem Cells on Immunohistochemical Patterns and Gene Expression of Metalloproteinases and Their Tissue Inhibitors in Doxorubicin Cardiomyopathy in a Rabbit Model

Aupperle¹,

Garbade

Schubert

et al. 2007

Vet Pathol

View full text Add to dashboard Cite

Abstract. This study aims to investigate the expression of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in chronic doxorubicin cardiomyopathy in a rabbit model and to evaluate the effects of bone marrow-derived mesenchymal stem cell (MSC) transplantation in this disease. Thirtynine 3-month-old New Zealand rabbits were divided into 4 groups: group 1 (n 5 9) was the untreated control. Groups 2-4 were treated with 6 weeks of doxorubicin (3 mg/kg). Group 2 (n 5 6) received no further treatment. In group 3 (n 5 9), animals were treated with culture medium (CM) alone. In group 4 (n 5 15), autologous MSCs (1.5-2.0 3 10 6 /ml) were injected in the left ventricular (LV) wall. Hearts were stained with HE and picrosirius red. MMP-1, -2, -3 and -9 and TIMP-2 and -3 were detected immunohistochemically. The mRNA levels were determined by real-time polymerase chain reaction. The results confirmed that doxorubicin treatment resulted in minimal myocardial fibrosis and showed that expression of MMPs increased and TIMP-3 decreased. The injection procedure resulted in increased myocardial fibrosis in groups 3 and 4. After MSC injection, MMP-1, MMP-2, and TIMP-3 expression was higher than that in group 2. CM injection led to more fibrosis, elevated TIMP-3, but diminished MMP-1 and MMP-2 expression compared with MSC injection. The mRNA levels of MMPs and TIMPs were not significantly different among all groups. In conclusion, chronic doxorubicin cardiomyopathy was characterized by increased MMP and decreased TIMP-3 expression. MSCs injection into the LV resulted in marked differences of collagen content and MMP/TIMP expression in the whole heart, although significant numbers of living MSCs were not detected after 4 weeks.

show abstract

“…We focused on the evaluation of the amount of inflammatory cells infiltrating the myocardium between day 0 and day 7 post-MI as it is well established that healing process of the myocardium takes place mainly during this time frame. Indeed, leukocytes invade the myocardial wound within the first day post-MI and regulate extracellular matrix metabolism through the synthesis of matrix metalloproteinases (MMPs), cytokines, and growth factors (9,31,32). In particular, neutrophils migrate to the site of ischemia 24-48 h post-MI followed by monocytes to participate in removal of necrotic cardiomyocytes (33).…”

Section: Discussionmentioning

confidence: 99%

Induction of Cardiac Angiogenesis Requires Killer Cell Lectin-Like Receptor 1 and α4β7 Integrin Expression by NK Cells

Bouchentouf

Forner

Cuerquis

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

Recent findings indicate that NK cells are involved in cardiac repair following myocardial infarction. The aim of this study is to investigate the role NK cells in infarct angiogenesis and cardiac remodeling. In normal C57BL/6 mice, myelomonocytic inflammatory cells invaded infarcted heart within 24 h followed by a lymphoid/NK cell infiltrate by day 6, accompanied by substantial expression of IL-2, TNF-α, and CCL2. In contrast, NOD SCID mice had virtually no lymphoid cells infiltrating the heart and did not upregulate IL-2 levels. In vitro and in vivo, IL-2–activated NK cells promoted TNF-α–stimulated endothelial cell proliferation, enhanced angiogenesis and reduced fibrosis within the infarcted myocardium. Adoptive transfer of IL-2–activated NK cells to NOD SCID mice improved post-myocardial infarction angiogenesis. RNA silencing technology and neutralizing Abs demonstrated that this process involved α4β7 integrin/VCAM-1 and killer cell lectin-like receptor 1/N-cadherin–specific binding. In this study, we show that IL-2–activated NK cells reduce myocardial collagen deposition along with an increase in neovascularization following acute cardiac ischemia through specific interaction with endothelial cells. These data define a potential role of activated NK cells in cardiac angiogenesis and open new perspectives for the treatment of ischemic diseases.

show abstract

Selective Matrix Metalloproteinase Inhibition Reduces Left Ventricular Remodeling but Does Not Inhibit Angiogenesis After Myocardial Infarction

Cited by 178 publications

References 37 publications

Matrix metalloproteinases in cardiovascular disease

Matrix metalloproteinases in cardiovascular disease

Effects of Autologous Stem Cells on Immunohistochemical Patterns and Gene Expression of Metalloproteinases and Their Tissue Inhibitors in Doxorubicin Cardiomyopathy in a Rabbit Model

Induction of Cardiac Angiogenesis Requires Killer Cell Lectin-Like Receptor 1 and α4β7 Integrin Expression by NK Cells

Contact Info

Product

Resources

About