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(a) Thinning, side-chain disappearance (Elastica van Gieson ×400) and (b) fragmentation of elastic laminae of the aortic media (Elastica van Gieson ×400). (c) Proliferation of Alcian blue-positive acid mucopolysaccharide was observed, usually adjacent to the dissection (Alcian blue ×100).
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Extensive clinicopathological analyses of aortic dissection have implicated hypertension and genetic abnormalities as the major pathogenic mechanisms. However, previous findings from pathological examinations have often been inconsistent with these mechanisms. In this paper, we suggest a significant role for the vasa vasorum in the aet...
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Context 1
... erythrocyte extravasation ( Fig. 3a-d). In 16 patients (76.2%), however, erythrocyte extravasation caused a large haematoma with thrombus formation (Fig. 1). Around the site of dissection, the elastic lamella was often thinned, with disappearance of its side-chain (11 patients, 52.4%), or showed fragmentation of lamellae (seven patients, 33.3%; Fig. 4a and b), and the interstitial acid mucopolysaccharide (Alcian blue-positive mucoid substance) level was increased in almost all patients (Fig. ...
Context 2
... (Fig. 1). Around the site of dissection, the elastic lamella was often thinned, with disappearance of its side-chain (11 patients, 52.4%), or showed fragmentation of lamellae (seven patients, 33.3%; Fig. 4a and b), and the interstitial acid mucopolysaccharide (Alcian blue-positive mucoid substance) level was increased in almost all patients (Fig. ...
Context 3
... medial changes. Eighteen patients (85%) had clear abnormalities in the elastic laminae, including fragmentation, thinning and disappearance of the side-chain ( Fig. 4a and b). The medial smooth muscle cells tended to be atrophic and to secrete acid mucopolysaccharide, mostly along the site of dissection (Fig. 4c). One case of aortic dissection with a bicuspid aortic valve was somewhat different from the other cases. It was the only case of dissection in only the middle of the media, where some mucin lakes ...
Context 4
... medial changes. Eighteen patients (85%) had clear abnormalities in the elastic laminae, including fragmentation, thinning and disappearance of the side-chain ( Fig. 4a and b). The medial smooth muscle cells tended to be atrophic and to secrete acid mucopolysaccharide, mostly along the site of dissection (Fig. 4c). One case of aortic dissection with a bicuspid aortic valve was somewhat different from the other cases. It was the only case of dissection in only the middle of the media, where some mucin lakes were present. This presentation is similar to the medial degeneration in Marfan syndrome (Fig. 1). Atheroma. Ten patients (48%) had no ...
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Citations
... Intimal necrosis renders dissection of the aorta. Osada et al. reported that aortic dissection in the outer third of the media is related to the significance of vasa vasorum in the triggering process [54]. If the authors dare to state tentative values, a basal value in the CAVI > 10 may expect to have advanced stages of arteriosclerosis with vulnerable plaque, which is close to the mean CAVI value (7.84) in Japanese + 2 × standard deviation (2 × 1.07). ...
A warning sign for impending cardiovascular events is not fully established. In the process of plaque rupture, the formation of vulnerable plaque is important, and oxidized cholesterols play an important role in its progression. Furthermore, the significance of vasa vasorum penetrating the medial smooth muscle layer and being rich in atheromatous lesions should be noted. The cardio-ankle vascular index (CAVI) is a new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle. The CAVI reflects functional stiffness, in addition to structural stiffness. The rapid rise in the CAVI means medial smooth muscle cell contraction and strangling vasa vasorum. A rapid rise in the CAVI in people after a big earthquake, following a high frequency of cardiovascular events has been reported. There are several cases that showed a rapid rise in the CAVI a few weeks or months before suffering cardiovascular events. To explain these sequences of events, we proposed a hypothesis: a rapid rise in the CAVI means medial smooth muscle contraction, strangling vasa vasorum, leading to ischemia and the necrosis of vulnerable plaque, and then the plaque ruptures. In individuals having a high CAVI, further rapid rise in the CAVI might be a warning sign for impending cardiovascular events. In such cases, treatments to decrease the CAVI better be taken soon.
... Of the total wall thickness, a fraction of 75% was assumed to correspond to the media and 25% to the adventitia (Humphrey 2013;Weisbecker et al. 2012). The false lumen is implemented in the cylindrical reference geometry by integrating unconnected elements at 70% of the medial layer, thus in the outer third of the media, and comprises 245° of the circumference, a value retrieved from a patient CT scan and in correspondence to Brunet et al. (2023) (Osada et al. 2013). The CT scan was acquired from the University Hospital of Düsseldorf with consent of the local ethical committee (reference number: 2017064325) (Logghe et al. 2021). ...
While transitioning from the acute to chronic phase, the wall of a dissected aorta often expands in diameter and adaptations in thickness and microstructure take place in the dissected membrane. Including the mechanisms, leading to these changes, in a computational model is expected to improve the accuracy of predictions of the long-term complications and optimal treatment timing of dissection patients. An idealized dissected wall was modeled to represent the elastin and collagen production and/or degradation imposed by stress- and inflammation-mediated growth and remodeling, using the homogenized constrained mixture theory. As no optimal growth and remodeling parameters have been defined for aortic dissections, a Latin hypercube sampling with 1000 parameter combinations was assessed for four inflammation patterns, with a varying spatial extent (full/local) and temporal evolution (permanent/transient). The dissected membrane thickening and microstructure was considered together with the diameter expansion over a period of 90 days. The highest success rate was found for the transient inflammation patterns, with about 15% of the samples leading to converged solutions after 90 days. Clinically observed thickening rates were found for 2–4% of the transient inflammation samples, which represented median total diameter expansion rates of about 5 mm/year. The dissected membrane microstructure showed an elastin decrease and, in most cases, a collagen increase. In conclusion, the model with the transient inflammation pattern allowed the reproduction of clinically observed dissected membrane thickening rates, diameter expansion rates and adaptations in microstructure, thus providing guidance in reducing the parameter space in growth and remodeling models of aortic dissections.
... Continuous positive airway pressure therapy for sleep apnea syndrome decreases CAVI [refer to 15]. Waon therapy, in which patients are placed in a dry sauna at 60 degree for 15 minutes, improves CAVI [57]. ...
A warning sign for impending cardio-vascular events is not fully established. In the process to plaque rupture, formation of vulnerable plaque is important, and oxidized cholesterols play important role in its progression. Furthermore, the significance of vasa vasorum penetrating medial smooth muscle layer and rich in atheromatous lesion should be paid attention. Cardio-ankle vascular index (CAVI) is new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle. CAVI reflects functional stiffness in addition to structural stiffness. Rapid rise of CAVI means medial smooth muscle cell contraction, and strangling vasa vasorum. We reported rapid rise of CAVI in peoples after big earthquake, following high frequency of cardiovascular events. And we met several cases who showed rapid rise of CAVI a few weeks or months before suffering cardiovascular events. To explain these sequences of events, we proposed a hypothesis; A rapid rise of CAVI means medial smooth muscle contraction, strangling vasa vasorum, leading ischemia, necrosis of vulnerable plaque, then, the plaque ruptures. In individuals having high CAVI, further rapid rise of CAVI might be a warning sign for impending cardiovascular events. In such case, treatments to decrease CAVI had better to be taken soon.
... These processes are constantly interacting with each other. In a study, Osada H. et al. (2013) examined samples of aortic aneurysm taken from 21 patients and concluded that damage to vasa vasorum leads to the development of medial necrosis and the subsequent rupture of the aortic aneurysm [1]. Similar conclusions were reached by Angouras D.S. (2013) and Tanaka H. (2017) [2,3]. ...
... These processes are constantly interacting with each other. In a study, Osada H. et al. (2013) examined samples of aortic aneurysm taken from 21 patients and concluded that damage to vasa vasorum leads to the development of medial necrosis and the subsequent rupture of the aortic aneurysm [1]. Similar conclusions were reached by Angouras D.S. (2013) and Tanaka H. (2017) [2,3]. ...
... The role of vasa vasorum in the pathogenesis of aortic aneurysm has been proven by clinical and animal studies [1,8]. In 2013, it was shown that impaired blood flow in the vasa vasorum system leads to the development of aortic aneurysm and further dissection [1]. ...
It is known that vasa vasorum contributes substantially to the blood supply and nutrition of one-third of the wall of the ascending thoracic aorta. Therefore, we focused on studying the relationship between inflammatory cells and vasa vasorum vessels in patients with aortic aneurysm. The material for the study was biopsies of thoracic aortic aneurysms taken from patients during an aneurysmectomy (34 men, 14 women, aged 33 to 79 years). The biopsies belonged to patients with non-hereditary thoracic aortic aneurysm. An immunohistochemical study was carried out using antibodies to antigens of T cells (CD3, CD4, CD8); macrophages (CD68); B cells (CD20); endothelium (CD31, CD34, von Willebrand factor (vWF)); and smooth muscle cells (alpha actin). Samples without inflammatory infiltrates contained less vasa vasorum in the tunica adventitia than samples with inflammatory infiltrates, and this difference was statistically significant p < 0.05. T cell infiltrates in the adventitia of aortic aneurysms were found in 28 of 48 patients. In the vessels of the vasa vasorum, surrounded by inflammatory infiltrates, T cells that adhered to the endothelium were found. The same cells were also localized in the subendothelial area. The number of adherent T cells in patients with inflammatory infiltrates in the aortic wall dominated the number of these cells in patients without inflammation of the aortic wall. This difference was statistically significant, p < 0.0006. Hypertrophy and sclerosis of the arteries of the vasa vasorum system, the narrowing of their lumen, and, as a result, impaired blood supply to the aortic wall, were found in 34 patients with hypertension. In 18 patients (both in patients with hypertension and in patients without hypertension), T cells that adhered to the vasa vasorum endothelium were found. In nine cases, massive infiltrates of T cells and macrophages were found, which surrounded and squeezed the vasa vasorum, preventing blood circulation. In six patients, parietal and obturating blood clots were found in the vasa vasorum vessels, which disrupted the normal blood supply to the aortic wall. We believe that this indicates the importance of the state of the vessels of the vasa vasorum in the development of an aortic aneurysm. In addition, pathological changes in these vessels may not always play a primary role, but always a very important role, in the pathogenesis of this disease.
... The causal event in CAD is an initial intimal tear that allows for the blood to accumulate in the media (inside-out mechanism). As Osada et al. noted, another important observation was the relative similar location of the dissection plane (in the outer media), which is nearly co-localized with the plane of the VV network in the outer media [34]. Also, the vascular network structure is a weak area within the aortic wall allowing the blood dissection to progress in the damaged media. ...
... They suggested that dysfunction of the vasa vasorum might play a key role in prolonged ischemia or malnutrition of the aortic media, resulting in necrotic layer formation in the dissecting aneurysm. 30 ...
Kazuhiro Shimizu,1 Mao Takahashi,1 Shuji Sato,1 Atsuhito Saiki,1 Daiji Nagayama,1,2 Takashi Hitsumoto,3 Akira Takahara,4 Kohji Shirai1,5 1Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Chiba, Japan; 2Department of Internal Medicine, Nagayama Clinic, Oyama, Tochigi, Japan; 3Hitsumoto Medical Clinic, Shimonoseki, Yamaguchi, Japan; 4Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, Japan; 5Department of Internal Medicine, Seijinkai Mihama Hospital, Chiba, Chiba, JapanCorrespondence: Kazuhiro Shimizu, Department of Internal Medicine, Toho University Sakura Medical Center, 561-4 Shimoshizu, Sakura, Chiba, 285-8741, Japan, Tel +81-43-462-8811, Fax +81-43-462-8820, Email k432@sakura.med.toho-u.ac.jpAbstract: Predictive factors for vascular events have not been established. The vasculature of the atheroma is supplied by penetration of the vasa vasorum through the smooth muscle cell layer from the adventitia. Smooth muscle cell contraction induces compression of the vasa vasorum, resulting in ischemia in intimal atheromatous lesions. Cardio-ankle vascular index (CAVI) has become known as an index of arterial stiffness of the arterial tree from the origin of the aorta to the ankle. CAVI reflects the progress of arteriosclerosis, and a rapid rise in CAVI indicates arterial smooth muscle cell contraction. We hypothesized that rapidly increased arterial stiffness evaluated by CAVI may be a predictor of impending cardiovascular events.Keywords: arterial stiffness, stress, plaque rupture, CAVI
... In addition, hypertension has a long-term effect on the Inner and one-third depth of the external media [18], where AD primarily occurs [19]. ...
Background:
The mortality of acute aortic dissection (AD) can reach 65~70%. However, it is challenging to follow the progress of AD formation. The purpose of this work was to observe the process of dissection development using a novel tear-embedded silicone phantom.
Methods:
Silicone phantoms were fabricated by embedding a torn area and primary tear feature on the inner layer. CT scanning and laser lightening were conducted to observe the variations in thickness and volume of the true lumen (TL) and false lumen (FL) during development.
Results:
The model with a larger interlayer adhesion damage required a lower pressure to trigger the development of dissection. At the initiation stage of dissection, the volume of TL increased by 25.5%, accompanied by a 19.5% enlargement of tear size. The force analysis based on the change of tear size verified the deduction of the process of interlaminar separation from the earlier studies.
Conclusions:
The primary tear and the weakening adhesion of the vessel layers are key factors in AD development, suggesting that some forms of primary damage to the arterial wall, in particular, the lumen morphology of vessels with straight inner lumen, should be considered as early risk predictors of AD.
... In humans, aortic medial pathologies, such as a loss of SMCs and collagen deposition, exhibit a gradient across the media that increases from the luminal to the adventitial aspects [23,32]. Aortic dissection occurs preferentially in the outer third of the aortic media [50]. Multiple TAA mouse models also exhibit outer media-dominant pathologies, such as thickening and hemorrhage ( Figure 1B) [32,[51][52][53]. ...
Smooth muscle cells (SMCs) are the major cell type of the aortic wall and play a pivotal role in the pathophysiology of thoracic aortic aneurysms (TAAs). TAAs occur in a region-specific manner with the proximal region being a common location. In this region, SMCs are derived embryonically from either the cardiac neural crest or the second heart field. These cells of distinct origins reside in specific locations and exhibit different biological behaviors in the complex mechanism of TAAs. The purpose of this review is to enhance understanding of the embryonic heterogeneity of SMCs in the proximal thoracic aorta and their functions in TAAs.
... The authors also described a detachment of layers near the adventitia-media border. These observations led to the notion that a mechanical defect due to tissue remodeling predisposes the aorta to dissection, a theory supported by vasa vasorum alterations observed in human aneurysmal specimens (43) and dissected specimens (145) and by the typical location of dissection near the adventitia-media border. Occlusion of the porcine vasa vasorum of the descending thoracic aorta led to "ischemic necrosis" in the outer aortic media evidenced by localized SMC loss and areas of elastin interspersed with fragmented elastin fibers (144). ...
... Studies centered on human ascending aortic specimens support the theory of vasa vasorum involvement in aortic disease including aneurysm and dissection. Osada et al. (145) considered specimens from 21 patients undergoing aortic replacement operation due to either Stanford type A (n = 20) or Stanford type B (n = 1) dissection. The researchers located dissection tears in the outer third of the aortic media and adventitial inflammation and thickening. ...
... Research initiatives from the author's laboratory enthusiastically support a fresh perspective of the adventitia in aortic biology and agree with writings by Kessler et al. (172), Osada et al. (145), and others (15,173) that this important blood vessel layer directly affects medial biology and deserves our attention and inquiry to delineate previously unknown aortic disease mechanisms. Work by the author's team in human aneurysmal specimens partially agree with the findings of Kessler et al. (172), with respect to decreased Vegf and elevated thrombospondin 1 (TSP1), although this was found in the adventitia rather than the aortic media (43). ...
The vasa vasorum are a vital microvascular network supporting the outer wall of larger blood vessels. Although these dynamic microvessels have been studied for centuries, the importance and impact of their functions in vascular health and disease are not yet fully realized. There is now rich knowledge regarding what local progenitor cell populations comprise and cohabitate with the vasa vasorum and how they might contribute to physiological and pathological changes in the network or its expansion via angiogenesis or vasculogenesis. Evidence of whether vasa vasorum remodeling incites or governs disease progression or is a consequence of cardiovascular pathologies remains limited. Recent advances in vasa vasorum imaging for understanding cardiovascular disease severity and pathophysiology open the door for theranostic opportunities. Approaches that strive to control angiogenesis and vasculogenesis potentiate mitigation of vasa vasorum-mediated contributions to cardiovascular diseases and emerging diseases involving the microcirculation.
... ATAAD is a life-threatening cardiovascular event that requires immediate surgical repair [8]. Aortic dissection results from the separation of the aortic wall layers, and a tear in the intimal layer allows blood to enter the tunica media, which causes progressive dissection [9]. Aortic calcifications extending from the aortic intima to the media may prevent progression of aortic dissection by restricting the separation [10]. ...
... Blumenthal et al. studied the relationship between age and the amounts of calcium in the intima and media of 540 human aortic specimens and found that calcifications were more common in the tunica media than in the intima at all ages [29]. Moreover, pathological examinations have indicated that aortic dissection initially develops in the tunica media [9]. Therefore, aortic calcifications present between the intima and the tunica media may prevent separation of these aortic wall layers and consequently reduce progression of the aortic dissection. ...
Aortic calcification in the tunica media is correlated with aortic stiffness, elastin degradation, and wall shear stress. The study aim was to determine if aortic calcifications influence disease progression in patients with acute type A aortic dissection (ATAAD). We retrospectively reviewed a total of 103 consecutive patients who had undergone surgery for ATAAD at our institution between January 2009 and December 2019. Of these, 85 patients who had preoperatively undergone plain computed tomography angiography (CTA) for evaluation of their aortic calcification were included. Moreover, we assessed the progression of aortic dissection after surgery via postoperative CTA. Using a classification and regression tree to identify aortic Agatston score thresholds predictive of disease progression, the patients were classified into high-score (Agatston score ≥ 3344; n = 36) and low-score (<3344; n = 49) groups. Correlations between aortic Agatston scores and CTA variables were assessed. Higher aortic Agatston scores were significantly correlated with the smaller distal extent of aortic dissection ( p < 0.001), larger true lumen areas of the ascending ( p = 0.009) and descending aorta ( p = 0.002), and smaller false lumen areas of the descending aorta ( p = 0.028). Patients in the high-score group were more likely to have DeBakey type II dissection ( p = 0.001) and false lumen thrombosis ( p = 0.027) than those in the low-score group, thereby confirming the correlations. Aortic dissection in the high-score group was significantly less distally extended ( p < 0.001). A higher aortic Agatston score correlates with the larger true lumen area of the ascending and descending aorta and the less distal progression of aortic dissection in patients with ATAAD. Interestingly, the findings before and after surgery were consistent. Hence, aortic Agatston scores are associated with aortic dissection progression and may help predict postoperative residual dissected aorta remodeling.
