Gene Expression Profiles in the Acutely Dissected Human Aorta

Müller, Bárbara; Modlich, Olga; Prisack, Hans-Bernd; Bojar, Hans; Schipke, Jochen D.; Goecke, Timm O.; Feindt, P.; Petzold, Thomas; Gams, E.; Müller, Wolfram; Hort, W; Sandmann, W.

doi:10.1053/ejvs.2002.1731

Cited by 54 publications

(56 citation statements)

References 28 publications

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“…Gene expression and gene network analyses revealed that aortic stress first induces a proliferative response, then an inflammatory response in the aortic walls, and finally visible pathological changes. These findings are consistent with findings in human AD 18. Continued aortic stress activates proliferative and inflammatory responses, and these responses occur in parallel with the development of focal medial disruption to the aorta 15.…”

Section: Discussionsupporting

confidence: 91%

Role of Macrophage Socs3 in the Pathogenesis of Aortic Dissection

Ohno‐Urabe

Aoki

Nishihara

et al. 2018

JAHA

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BackgroundAortic dissection (AD) is a life‐threatening medical emergency caused by the abrupt destruction of the intimomedial layer of the aortic walls. Given that previous studies have reported the involvement of proinflammatory cytokine interleukin‐6 in AD pathogenesis, we investigated the role of signal transduction and activator of transcription 3 signaling, a downstream pathway of interleukin‐6 in macrophages in pathogenesis of AD.Methods and ResultsWe characterized the pathological and molecular events triggered by aortic stress, which can lead to AD. Aortic stress on the suprarenal aorta because of infrarenal aorta stiffening and angiotensin II infusion for 1 week caused focal medial rupture at the branching point of the celiac trunk and superior mesenteric artery. This focal medial rupture healed in 6 weeks in wild‐type (WT) mice, but progressed to AD in mice with macrophage‐specific deletion of Socs3 gene (mSocs3‐KO). mSocs3‐KO mice showed premature activation of cell proliferation, an inflammatory response, and skewed differentiation of macrophages toward the tissue‐destructive phenotype. Concomitantly, they showed aberrant phenotypic modulation of smooth muscle cells and transforming growth factor beta signaling, which are likely to participate in tissue repair. Human AD samples revealed signal transduction and activator of transcription 3 activation in adventitial macrophages adjacent to the site of tissue destruction.ConclusionsThese findings suggest that AD development is preceded by focal medial rupture, in which macrophage Socs3 maintains proper inflammatory response and differentiation of SMCs, thus promoting fibrotic healing to prevent tissue destruction and AD development. Understanding the sequence of the pathological and molecular events preceding AD development will help predict and prevent AD development and progression.

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Section: Discussionsupporting

confidence: 91%

Role of Macrophage Socs3 in the Pathogenesis of Aortic Dissection

Ohno‐Urabe

Aoki

Nishihara

et al. 2018

JAHA

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“…Pathologic studies of acute aortic dissection revealed infiltration of macrophages and leukocytes and increased expression of several genes associated with inflammatory processes, such as interleukin (IL)-6 and IL-8, in the dissected aorta. 18,19 These findings suggested that local aortic insult caused by acute aortic dissection has the potential to produce humoral factors that pass through the pulmonary vasculature and activate both resident leukocytes and the pulmonary vascular endothelium. Sugano et al noted that the powerful insult of intimal rupture and propagation of the dissection into the media might provoke activation of the cellular and humoral inflammatory systems and lead to impaired oxygenation.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Prolonged Mechanical Ventilation Following Surgery for Acute Type A Aortic Dissection

Kimura

Tanaka

Kawahito

et al. 2008

Circ J

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ompared to the relatively favorable in-hospital outcomes of acute type B aortic dissection, 1,2 acute type A aortic dissection (AAAD) remains one of the most serious cardiovascular diseases associated with a high mortality. The latest report from the International Registry of Acute Aortic Dissection Investigators group indicated that in-hospital mortality remains high (163 of 682 patients (23.9%) with AAAD treated surgically between 1996 and 2003). 3 With such critical illness, some patients require prolonged mechanical ventilation (PMV) after surgery. Compared with patients who undergo other cardiac surgeries, patients with AAAD are more likely to suffer preoperative hemodynamic instability, organ malperfusion, and prolonged cardiopulmonary bypass (CPB) during surgery. In addition, re-exploration for bleeding and neurological deficits are common postoperative complications in these patients. 4 All these factors can contribute to PMV after AAAD surgery. 5 Another factor related to the PMV is systemic inflammatory response-related lung injury evoked by acute aortic dissection. 6,7 A number of studies regarding PMV following cardiac surgery have examined its predictors or its influence on clinical outcomes and costs. [8][9][10][11][12][13][14][15][16][17] However, little is known about PMV following AAAD surgery. The aim of this retrospective study was to identify predictors of PMV following AAAD surgery and to assess the influence of PMV on the short and long-term postoperative courses. MethodsFrom January 1997 through to December 2006, 243 consecutive patients with AAAD underwent emergency surgery at our hospital. Aortic dissection was diagnosed by means of enhanced computed tomography scan or echocardiography, and transesopageal echocardiography was used for confirmation when possible. In all patients, emergency surgery was performed within 14 days after the onset of symptoms; 90% of these surgeries were performed within 48 h. So that we could focus on PMV, 10 patients who died within 48 h after surgery were excluded from the study. Death within 48 h after surgery was due to profound cardiac failure (8 patients) or refractory bleeding (2 patients). The remaining 233 patients (120 men, 113 women, mean age: 63.4±11.2 years) were divided into 2 groups according to the duration of mechanical ventilation: those who were tracheally extubated within 48 h after admission to the intensive care unit (ICU) (group A, n=149) and those who required mechanical ventilation for more than 48 h (group B, n=84). Patients who were reintubated within 24 h after extubation were considered to have an interrupted period of ventilation. To identify the independent predictors for PMV, we compared 48 perioperative factors (25 preoperative factors and 23 intra or postoperative factors) between the 2 groups. Mortality and morbidity, length of the ICU and hospital stays, and long-term survival were compared

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“…Patients with connective tissue disorders, such as Marfan syndrome, or familial forms of TAA were excluded from these studies, so they do not provide insight into molecular mechanisms of aneurysm progression in these cases. Additionally, no significant gene expression differences were found when tissue from normal and diseased aortic regions were compared from the same TAA patient (9,58), so these studies do not give information about why aneurysms develop in specific vascular locations. Schwill et al (69) investigated changes in aortic gene expression for a Marfan mouse model (mgR) and found increases in inflammatory pathway genes, consistent with our results.…”

Section: Regulated In Fbln4mentioning

confidence: 97%

“…Emr1 and Ptgs2 may represent targets to ameliorate the inflammatory response and limit the diameter expansion in Fbln4 Ϫ/Ϫ AA. It has been shown previously that diseased aortic tissue from TAA patients has different gene expression patterns than normal aortic tissue from control patients (1,9,43,58). Patients with connective tissue disorders, such as Marfan syndrome, or familial forms of TAA were excluded from these studies, so they do not provide insight into molecular mechanisms of aneurysm progression in these cases.…”

Section: Regulated In Fbln4mentioning

confidence: 99%