The Multitasking Role of Macrophages in Stanford Type A Acute Aortic Dissection

Abstract

Objectives: The aim of the study was to determine whether the release by macrophages of matrix metalloproteinase (MMP)-12 and vascular endothelial growth factor (VEGF) - leading to inflammation, matrix degradation and neoangiogenesis - represents an effective pathway that underlies aortic wall remodeling in Stanford type A acute aortic dissection (AAD). Methods: Twenty-one consecutive patients with no genetic predisposition, with Stanford type A AAD were selected. In each patient, the levels of serum VEGF, MMP-12, serum interleukin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1 were evaluated using enzyme-linked immunosorbent assay. Ascending aortic specimens were collected for immunohistochemical identification of any presence of inflammatory infiltrate, VEGF and CD31 expression. Results: A significant increase in serum VEGF (p = 0.044), MMP-12 (p = 0.007), IL-6 (p = 0.0001), IL-8 (p = 0.0001) and MCP-1 (p = 0.0001) levels was observed in the AAD group compared to the control group. Furthermore, all AAD samples were positive for VEGF in the tunica media and showed vessel growth and immune-inflammatory infiltrate. A large number of cases (62.79%) showed inflammation at the edge of the dissection and approximately half (51.42%) showed neovessels growing at the edge of the dissection. Conclusions: The results suggest that VEGF-mediated angiogenesis and matrix degradation play a role in AAD. Finally, we believe that MMP-12 should be considered a marker of AAD.

Balance between Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases

“…A 1:1 molecular ratio between MMPs and TIMPs maintains the structural integrity of the aorta by regulating the degradation and synthesis of the extracellular matrix [3,4]. Although MMP-12 has been implicated in many pathological processes, such as aortic aneurysms and dissections, atherosclerotic plaque progression, emphysema and cancer, it is regarded as a specific marker of aortic dissection [4,5]. Even though there is no specific TIMP for MMP-12, it is conceivable that evaluating TIMPs as well as the MMP/TIMP ratio could be helpful in determining the mechanism underlying aortic dissections and the usefulness of new markers more precisely.…”

The Role of the Macrophage in the Development of Aortic Dissection

“…In this issue of Cardiology , Del Porto et al [2] evaluated the role of the macrophage in the development of Stanford type A aortic dissections. The investigators aimed to determine whether macrophage release of metalloperoxidase MMP-12 and vascular endothelial growth factor (VEGF) led to inflammation and matrix degradation in 21 patients who presented with acute Stanford type A aortic dissection.…”

“…In their report, Del Porto et al [2] addressed the role that MMP-12, in particular, plays in the degradation of elastin, fibronectin, and collagen leading to the development of thoracic aortic dissection, and hypothesized that MMP-12, in addition to VEGF and MCP-1 is a potentially measureable prediction molecule and hopefully clinically targetable in the future to prevent thoracic aortic aneurysms. …”

“…The study of Del Porto et al [2] does have some limitations. It is known that thoracic aortic aneurysms and dissections may appear in patients with some form of familial or genetic predisposition.…”

“…In summary, the importance and gist of the study of Del Porto et al [2 ]lie in the fact that it highlights the importance of several proteins involved in the interstitial environment of thoracic aortic disease. The authors' work is only one step forward in identifying such endopeptidases and other potential biochemical markers that may eventually lead to therapeutic interventions that can change the course of one of the most acutely devastating and awe-inspiring diseases that face physicians today.…”