scholarly journals Smooth Muscle Cells Derived From Second Heart Field and Cardiac Neural Crest Reside in Spatially Distinct Domains in the Media of the Ascending Aorta—Brief Report

2017 ◽  
Vol 37 (9) ◽  
pp. 1722-1726 ◽  
Author(s):  
Hisashi Sawada ◽  
Debra L. Rateri ◽  
Jessica J. Moorleghen ◽  
Mark W. Majesky ◽  
Alan Daugherty
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Neural Crest ◽  
Muscle Cells ◽  
Ascending Aorta ◽  
Cardiac Neural Crest ◽  
Second Heart Field ◽  
Heart Field ◽  
The Media

scholarly journals Functional Role of Second Heart Field-derived Smooth Muscle Cells in Thoracic Aortopathies in Mice

2020 ◽  
Author(s):  
Hisashi Sawada ◽  
Hideyuki Higashi ◽  
Chen Zhang ◽  
Yanming Li ◽  
Yuriko Katsumata ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Smooth Muscle Cells ◽  
Neural Crest ◽  
Single Cell ◽  
Proteomic Analysis ◽  
Ascending Aorta ◽  
Second Heart Field ◽  
Heart Field

AbstractBackgroundThe ascending aorta is a common location for thoracic aortopathies. Pathology predominates in the aortic media with disease severity being most apparent in outer laminar layers. In the ascending aorta, smooth muscle cells (SMCs) are derived from two embryonic origins: cardiac neural crest and second heart field (SHF). SMCs of these origins have distinct distributions, and the localization of SHF coincides with the regional specificity in some forms of thoracic aortopathies. However, the role of SHF-derived SMCs in maintaining the structural and functional integrity of the ascending aorta remains unclear.MethodsMass spectrometry assisted proteomic and single cell transcriptomic analyses were performed in mouse aortas to discriminate molecular features of SHF-derived SMCs in maintaining the aortic homeostasis. Genetic deletion of low-density lipoprotein receptor-related protein 1 (Lrp1) or transforming growth factor-β receptor 2 (Tgfbr2) in SHF-derived SMCs was conducted to examine impact of SHF-derived SMCs on the development of thoracic aortopathies.ResultsProteomic analysis did not detect differences in protein profiles between ascending (disease prone) and descending (disease resistant) thoracic aortas in saline-infused mice. However, angiotensin II infusion altered these profiles in a region-specific manner. Angiotensin II evoked differential expression of multiple LRP1 ligands. Histological analysis demonstrated that angiotensin II-induced medial disruptions were detected mainly in outer laminar layers derived from the SHF. Single cell RNA sequencing using normal mouse aortas revealed lower abundance of elastin mRNA in SHF-derived SMCs compared to SMCs from the cardiac neural crest. In addition, Lrp1 and Tgfbr2 mRNA were abundant in SHF-derived SMCs. To examine biological effects of SHF-derived cells, Lrp1 or Tgfbr2 was deleted in SHF-derived cells in mice. SHF-specific Lrp1 deletion augmented angiotensin II-induced aortic aneurysm and rupture in the ascending region. Proteomic analysis discerned regulation of protein abundances related to TGF-β signaling pathways by Lrp1 deletion in SHF-derived cells. Deletion of Tgfbr2, a key regulator of TGF-β signaling, in SHF-derived cells led to embryonic lethality at E12.5 with dilatation of the outflow tract and retroperitoneal hemorrhage in mice.ConclusionThese results demonstrate that SMCs derived from the SHF play a critical role in the integrity of the ascending aortic wall.

scholarly journals Notch2 is required for the proliferation of cardiac neural crest-derived smooth muscle cells

2008 ◽  
Vol 237 (4) ◽  
pp. 1144-1152 ◽  
Author(s):  
Prajakta Varadkar ◽  
Matthew Kraman ◽  
Daryl Despres ◽  
Ge Ma ◽  
Julie Lozier ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Neural Crest ◽  
Muscle Cells ◽  
Cardiac Neural Crest

Abstract 128: LRP1 Deletion in Smooth Muscle Cells of the Outer Aortic Media Promotes Angiotensin II-induced Thoracic Aortic Aneurysm

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Hisashi Sawada ◽  
Debra L Rateri ◽  
Mark W Majesky ◽  
Alan Daugherty
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Smooth Muscle Cells ◽  
Thoracic Aortic Aneurysm ◽  
Aortic Rupture ◽  
Muscle Cells ◽  
Lineage Tracing ◽  
Second Heart Field ◽  
Heart Field

Objective: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional protein that is linked to several vascular pathologies. LRP1 deletion in smooth muscle cells (SMCs) accelerates angiotensin II (AngII)-induced thoracic aortic aneurysm (TAA). In association with TAA formation, there is medial thickening that is characterized by a transmural gradient in which pathology progressively increases from lumen to adventitial aspect. We hypothesized that deletion of LRP1 in the outer medial layers of the proximal thoracic aorta has a pivotal role in the pathogenesis of TAA. The aim of this study was to determine whether LRP1 deletion in the outer media accelerates AngII-induced TAA formation. Methods and Results: SMCs in the outer media of the ascending aorta are derived from the second heart field, as demonstrated by lineage tracing studies using Cre under the control of Mef2c. Therefore, we used Mef2c-driven Cre to delete LRP1 in SMCs of the outer medial layers. Female LRP1 flox/flox mice were bred to male Mef2c-Cre1/0 mice to generate study mice. We first confirmed LRP1 deletion in Cre1/0 mice by both immunostaining and Western blot. LRP1 was expressed ubiquitously across smooth muscle cells of all aortic medial layers in Cre 0/0 mice. In mice expressing Mef2c-Cre, aortic LRP1 protein was detected only in SMCs of the inner laminar medial layers. Western blotting demonstrated LRP1 protein abundance in Cre expressing mice was reduced by 43%. Saline or AngII (1,000 ng/kg/min) was infused by subcutaneous osmotic pumps for 28 days into 12 - 14 week-old male Cre0/0 and 1/0 mice. As expected, systolic blood pressure increased similarly in both AngII-infused Cre 0/0 and 1/0 mice compared to saline-infused mice. Aortic rupture occurred within 3 to 10 days after AngII infusion in 17% of AngII-infused Cre 0/0 mice, while LRP1 deletion in Cre 1/0 mice increased aortic rupture to 27%. Aortic diameter in the survivors was significantly increased in Cre1/0 mice compared to Cre0/0 mice. Histologically, elastin fragmentation was detected in the aorta of AngII-infused Cre 0/0 mice and greater in Cre1/0 mice. Conclusion: LRP1 in second heart field-derived SMCs of the outer media may play a critical role in the pathogenesis of TAA.

The cephalic neural crest provides pericytes and smooth muscle cells to all blood vessels of the face and forebrain

Development ◽  
2001 ◽  
Vol 128 (7) ◽  
pp. 1059-1068 ◽  
Author(s):  
H.C. Etchevers ◽  
C. Vincent ◽  
N.M. Le Douarin ◽  
G.F. Couly
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Neural Crest ◽  
Muscle Cells ◽  
Embryonic Cell ◽  
Avian Embryo ◽  
Connective Tissues ◽  
The Face ◽  
Mesodermal Origin ◽  
The Central Nervous System

Most connective tissues in the head develop from neural crest cells (NCCs), an embryonic cell population present only in vertebrates. We show that NCC-derived pericytes and smooth muscle cells are distributed in a sharply circumscribed sector of the vasculature of the avian embryo. As NCCs detach from the neural folds that correspond to the future posterior diencephalon, mesencephalon and rhombencephalon, they migrate between the ectoderm and the neuroepithelium into the anterior/ventral head, encountering mesoderm-derived endothelial precursors. Together, these two cell populations build a vascular tree rooted at the departure of the aorta from the heart and ramified into the capillary plexi that irrigate the forebrain meninges, retinal choroids and all facial structures, before returning to the heart. NCCs ensheath each aortic arch-derived vessel, providing every component except the endothelial cells. Within the meninges, capillaries with pericytes of diencephalic and mesencephalic neural fold origin supply the forebrain, while capillaries with pericytes of mesodermal origin supply the rest of the central nervous system, in a mutually exclusive manner. The two types of head vasculature contact at a few defined points, including the anastomotic vessels of the circle of Willis, immediately ventral to the forebrain/midbrain boundary. Over the course of evolution, the vertebrate subphylum may have exploited the exceptionally broad range of developmental potentialities and the plasticity of NCCs in head remodelling that resulted in the growth of the forebrain.

scholarly journals Histochemical and immunohistochemical analysis of ruptured atherosclerotic abdominal aortic aneurysm wall

2010 ◽  
Vol 67 (12) ◽  
pp. 959-964 ◽  
Author(s):  
Irena Tanaskovic ◽  
Aleksandra Mladenovic-Mihailovic ◽  
Slavica Usaj-Knezevic ◽  
Vesna Stankovic ◽  
Aleksandar Aleksic ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Smooth Muscle Cells ◽  
Periodic Acid ◽  
Muscle Cells ◽  
Foam Cells ◽  
Abdominal Aortic ◽  
S 100 ◽  
The Media

Background/Aim. The main complication of the atherosclerotic abdominal aortic aneurism (AAA) is her rupture that begins with lesion in intima and rupture. The purpose of this work was to determine immunocytochemical and morphofunctional characteristics of the cells in aortic wall in ruptured atherosclerotic abdominal aortic aneurysm. Method. During the course of this study, 20 samples of atherosclerotic AAA were analyzed, all of them obtained during authopsy. The samples were fixed in 4% formalin and embedded in paraffin. Sections of 5 ?m thickness were stained histochemically (of Heidenhain azan stain and Periodic acid Schiff - PAS stain) and immunocytochemically using a DAKO LSAB+/HRP technique to identify ?-smooth muscle actin (?-SMA), vimentin, myosin heavy chains (MHC), desmin, S-100 protein, CD45 and CD68 (DAKO specification). Results. The results of our study showed that ruptured atherosclerotic AAA is characterized by a complete absence of endothelial cells, the disruption of basal membrane and internal elastic lamina, as well as a presence of the remains of hypocellular complicated atherosclerotic lesion in intima. On the plaque margins, as well as in the media, smooth muscle cells (SMCs) are present, which express a ?-SMA and vimentin (but without MHC or desmin expression), as well as leukocyte infiltration, and a large number of foam cells. Some of the foam cells show a CD68-immunoreactivity, while the others show vimentin- and S-100 protein-immunoreactivity. Media is thinned out with a disorganized elastic lamellas, while adventitia is characterized by inflammatory inflitrate (infection). Conclusion. Rupture of aneurysm occurs from the primary intimal disruption, which spreads into thinned out media and adventitia. Rupture is caused by unstable atherom, hypocellularity, loss of contractile characteristics of smooth muscle cells in intima and media, neovascularization of the media, as well as by the activity of the macrophages in the lesion.

A Structure-Based Biomechanical Model for the Effect of Dissolution of Muscle Cells on Pig Arteries: Elastin Associated With Muscle and Extracellular Matrix

2011 ◽  
Author(s):  
Aristotelis Agianniotis ◽  
Alexander Rachev ◽  
Nikos Stergiopulos
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Biomechanical Model ◽  
Muscle Cells ◽  
In Series ◽  
Minor Part ◽  
The Media ◽  
The One ◽  
A Minor

We developed a structure-based model of the arterial wall to explain the effect of dissolution of smooth muscle cells (SMC) on the mechanical behavior of the artery and to obtain a better understanding of the interaction between the different wall components. Pressure-radius curves and dimensions of zero-stress configuration were measured in 5 control and 5 decellularized porcine common carotid arteries. We found that 13% of elastin is associated with the smooth muscle cells (SMC) whereas the rest 87% is associated with the extracellular matrix (ECM). Further, we found that the elastin related to SMC and the one related to the ECM have circumferential prestretches of 2.04 and 0.89, respectively. We conclude that the majority of elastic in the media is linked to ECM and is under compression at zero load, whereas a minor part is linked to VSM and is under tension (SMC related) at its zero load state. Upon chemical dissolution of the muscle cells elastin in series with SMC do not bear load allowing elastin connected to ECM to release its compressive prestress, leading to the expansion of the artery.

Bovine distal pulmonary arterial media is composed of a uniform population of well-differentiated smooth muscle cells with low proliferative capabilities

2003 ◽  
Vol 285 (4) ◽  
pp. L819-L828 ◽  
Author(s):  
Leopold Stiebellehner ◽  
Maria G. Frid ◽  
John T. Reeves ◽  
Robert B. Low ◽  
Meena Gnanasekharan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Pulmonary Circulation ◽  
Main Pulmonary Artery ◽  
Muscle Cells ◽  
Hypoxic Exposure ◽  
Growth Responses ◽  
The Media ◽  
Well Differentiated ◽  
Uniform Population

The media of the normal bovine main pulmonary artery (MPA) is composed of phenotypically heterogeneous smooth muscle cells (SMC) with markedly different proliferative capabilities in response to serum, mitogens, and hypoxia. Little, however, is known of the SMC phenotype in distal pulmonary arteries (PA), particularly in arterioles, which regulate the pulmonary circulation. With a panel of muscle-specific antibodies against α-smooth muscle (SM)-actin, SM-myosin heavy chains (SM-MHC), SM-MHC-B isoform, desmin, and meta-vinculin, we demonstrate a progressive increase in phenotypic uniformity and level of differentiation of SMC along the proximal-to-distal axis of normal adult bovine pulmonary circulation so that the media of distal PA (1,500- to 100-μm diameter) is composed of a phenotypically uniform population of “well-differentiated” SMC. Similarly, when isolated and assessed in vitro, distal PA-SMC is composed of a single, uniform population of differentiated SMC that exhibited minimal growth responses to a variety of mitogens while their cell size increased substantially in response to serum. Their growth was inhibited by hypoxic exposure under all conditions tested. Distal PA-SMC also differed from MPA-SMC by exhibiting a distinct pattern of DNA synthesis in response to serum and mitogens. Thus, in contrast to the MPA, distal PA media is composed of an apparently uniform population of well-differentiated SMC that are proliferation resistant and have a substantial capacity to hypertrophy in response to growth-promoting stimuli. We thus speculate that distinct SMC phenotypes present in distal vs. proximal PA may confer different response mechanisms during remodeling in conditions such as hypertension.

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