The Adventitia: Essential Regulator of Vascular Wall Structure and Function

Stenmark, Kurt R.; Yeager, Michael E.; Kasmi, Karim C. El; Nozik‐Grayck, Eva; Gerasimovskaya, Evgenia; Li, Min; Riddle, Suzette; Frid, Maria G.

doi:10.1146/annurev-physiol-030212-183802

Cited by 370 publications

(374 citation statements)

References 161 publications

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“…MOMA-2 staining revealing monocyte/ macrophage infiltration in aortic wall was determined in wild-type, endothelium-specific endothelin-1 overexpression (eET-1), colony stimulating actor-deficient (Csf1 cells), nerves, progenitor cells, and immune cells, including macrophages. 22 Perivascular fat is closely associated to the adventitia. Overexpression of ET-1 in endothelial cells caused an increase in monocyte/macrophage infiltration in the adventitia and associated perivascular fat, which is similar to findings in mice infused with Ang II or aldosterone.…”

Section: Csf1mentioning

confidence: 99%

“…Vascular inflammation could be initiated and perpetuated in the adventitia, according to the outside-in hypothesis. 22 Increased expression of ET-1 in endothelium or within the adventitia could act in paracrine fashion directly on monocytes or macrophages or via other cells, such as the smooth muscle cells. In this study and previously, we found that a deficiency in CSF1 impaired monocyte/macrophage infiltration induced by ET-1, Ang II, and DOCA/salt in rodents, the latter a hypertensive model with an important ET-1-dependent component.…”

Section: Csf1mentioning

confidence: 99%

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Reduced Macrophage-Dependent Inflammation Improves Endothelin-1–Induced Vascular Injury

Javeshghani

Barhoumi²,

Idris-Khodja³

et al. 2013

Hypertension

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E ndothelin-1 (ET)-1, a 21-aa peptide produced by endothelial and other cells, is one of the most potent vasoconstrictors.1,2 Plasma ET-1 is increased in patients with essential hypertension and in hypertension associated with systemic disorders, in atherosclerosis and heart failure, as well as in other cardiovascular and metabolic disorders, and in chronic kidney disease.3 ET-1 plays a role in the development of hypertension by causing vascular damage and inflammation. 4,5 Transgenic mice overexpressing ET-1 specifically in endothelial cells (eET-1) present endothelial dysfunction and vascular remodeling, oxidative stress, and inflammation. 6,7 The immune system plays a role in hypertension and vascular injury. [8][9][10] The innate immune system is involved in angiotensin (Ang) II, deoxycorticosterone acetate (DOCA)/ salt, and aldosterone-induced hypertension and vascular damage. [11][12][13] Ang II, DOCA/salt, and aldosterone infusion caused an increase in vascular monocyte/macrophage infiltration. Ang II and DOCA/salt-induced hypertension and vascular remodeling, oxidative stress, and inflammation were blunted in a model with reduced monocytes/ macrophages, the osteopetrotic (Op) mouse, which is deficient in macrophage colony stimulating factor (CSF) 11,12 because of a thymidine (T) insertion in the coding region of the colony stimulating factor (Csf1) gene that generates a stop codon 21 bp downstream.14 Similarly, aldosterone-induced endothelial dysfunction and vascular oxidative stress were decreased in Csf1Op/+ mice. 13 The innate immune system could play a role in ET-1-induced vascular injury, because the inflammation observed in eET-1 is characterized by an increase in vascular monocyte/macrophage infiltration. However, this remains to be demonstrated.To test the hypothesis that innate immunity participates in ET-1-induced vascular injury, we studied whether vascular injury induced by increased expression of ET-1 is prevented in eET-1 mice crossed with Csf1Op/+ mice that have reduced monocyte/macrophage-dependent inflammation.Abstract-Transgenic mice with endothelium-specific endothelin-1 (ET-1) overexpression exhibit endothelial dysfunction and vascular remodeling, oxidative stress, and inflammation. We previously observed that monocytes/macrophages play a role in angiotensin II, aldosterone, and deoxycorticosterone acetate/salt-induced vascular remodeling, oxidative stress, and inflammation using a model with reduced monocytes/macrophages, the osteopetrotic (Op) mouse, which has a mutation in the macrophage colony stimulating factor (Csf1) gene. However, it is unknown whether monocytes/ macrophages are implicated in adverse vascular effects of ET-1. We hypothesized that reduction in monocytes/ macrophages would blunt ET-1-induced vascular injury. We performed a study on 4-to 6-month-old male mice with endothelium-specific ET-1 overexpression (eET-1), reduction in CSF1 (Csf1Op/+ ), or both (eET-1/Csf1Op/+ ), and their wildtype littermate control mice. There was no difference in systolic blood pre...

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Section: Csf1mentioning

confidence: 99%

Section: Csf1mentioning

confidence: 99%

Reduced Macrophage-Dependent Inflammation Improves Endothelin-1–Induced Vascular Injury

Javeshghani

Barhoumi²,

Idris-Khodja³

et al. 2013

Hypertension

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“…4,5 During the remodeling, pulmonary adventitial fibroblasts (PAFs) are highly activated and undergo phenotype switch characterized by excessive proliferation, migratory, and inflammatory activity. 6,7 Therefore, inhibition of the aberrant activation of PAFs may reverse the remodeling process of pulmonary vascular adventitia and have therapeutic potential for HPH.…”

mentioning

confidence: 99%

miR-29a-3p Attenuates Hypoxic Pulmonary Hypertension by Inhibiting Pulmonary Adventitial Fibroblast Activation

et al. 2015

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H ypoxic pulmonary hypertension (HPH) is still a lifethreating disorder lack of effective agents. It is highly prevalent in advanced chronic obstructive pulmonary disease and high altitude hypoxia. With the increase of chronic obstructive pulmonary disease patients, the morbidity of HPH is rising. Although most of HPH is mild to moderate, a subpopulation (1%-4%) with grim prognosis present with severe pulmonary hypertension.1 Pharmacological agents moderately improve the symptoms and hemodynamic parameters of severe pulmonary hypertension, but none significantly reduces mortality. 2,3 There is a pressing need to identify novel target to treat HPH.One of the characteristics of HPH is the dramatic remodeling of pulmonary vascular adventitia. 4,5 During the remodeling, pulmonary adventitial fibroblasts (PAFs) are highly activated and undergo phenotype switch characterized by excessive proliferation, migratory, and inflammatory activity. 6,7 Therefore, inhibition of the aberrant activation of PAFs may reverse the remodeling process of pulmonary vascular adventitia and have therapeutic potential for HPH. 8 Increasing evidence shows that miRNAs, especially miR-29 family members, participate in the development of organ fibrosis via regulating the activation of fibroblasts. 9-11Downregulation of miR-29 underlies transforming growth factor-β-mediated pulmonary fibrosis, and overexpression of miR-29 inhibits bleomycin-induced pulmonary fibrosis. 12 Although PAFs in HPH undergo the similar activated phenotype to that in lung fibrosis, 6 the role of miR-29 family member in the hypoxia-induced activation of PAFs and the development of HPH is not known. On the other hand, hypoxia-inducible factor-1α (HIF-1α), a key transcription factor mediating cellular response to hypoxia, and Smad3, which can inhibit miR-29 expression in organ fibrosis, are interdependent in hypoxia. [13][14][15][16] Therefore, HIF-1α and Smad3 may be jointly involved in the regulation of miR-29 in the activation of PAFs in hypoxia.The present study explored the effects of miR-29a in the activation of PAFs in hypoxia and the therapeutic potential in HPH. The results show that miR-29a-3p plays a key role in hypoxia-induced activation of PAFs and has protective effects in HPH in rats.Abstract-Activation of pulmonary adventitial fibroblasts plays a key role in the pulmonary vascular remodeling in hypoxic pulmonary hypertension. Previous studies showed that miRNAs participated in the regulation of fibroblast activation. This study explored the role of miR-29 in the activation of pulmonary adventitial fibroblasts and the therapeutic potential in hypoxic pulmonary hypertension. We found that hypoxia-induced pulmonary adventitial fibroblasts activation was accompanied with a drastic decrease of miR-29a-3p expression. Knockdown of hypoxia-inducible factor-1 α or Smad3 reversed the hypoxia-induced decrease of miR-29-3p in cultured pulmonary adventitial fibroblasts. In vitro, miR-29a-3p mimic inhibited the hypoxia-induced proliferation, migration, and secretion of p...

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“…All the three layers of the arteries infected by the virus would show inflammatory cell infiltrate. The thickened adventitia is associated with inflammation of the vasa vasorum in the early VZV-vasculopathy [15,16]. These altered pathology lead to arterial caliber irregularities, and contractility Arterial or venous thrombosis of the lower libs due to VZVhypercoagulability.…”

Section: Resultsmentioning

confidence: 99%

Relationship of Coping Responses and Anxiety Symptoms in Hispanic Youth

Morales¹,

Jacobson²

2018

Acta Psychopathol

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This is a case of herpes zoster opthalmicus with involvement of the right trigeminal nerve presented with stroke and hemiplegia secondary to HZV vasculopathy. The author discusses clinical manifestation, the subtle diagnosis, and treatment of HZV vasculopathy. Anti-VZV antibodies along with the VZV-DNA sequencing using the new PCR technology are key to diagnosis when VZV infection presented without the typical rash.

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The Adventitia: Essential Regulator of Vascular Wall Structure and Function

Cited by 370 publications

References 161 publications

Reduced Macrophage-Dependent Inflammation Improves Endothelin-1–Induced Vascular Injury

Reduced Macrophage-Dependent Inflammation Improves Endothelin-1–Induced Vascular Injury

miR-29a-3p Attenuates Hypoxic Pulmonary Hypertension by Inhibiting Pulmonary Adventitial Fibroblast Activation

Relationship of Coping Responses and Anxiety Symptoms in Hispanic Youth

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