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Molecular regulation of arterial aneurysms : Role of actin dynamics and microRNAs in vascular smooth muscle

Published on Aug 10, 2017in Frontiers in Physiology 3.20
· DOI :10.3389/fphys.2017.00569
Azra Alajbegovic5
Estimated H-index: 5
(Lund University),
Johan Holmberg20
Estimated H-index: 20
(Lund University),
Sebastian Albinsson20
Estimated H-index: 20
(Lund University)
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Abstract
Aortic aneurysms are defined as an irreversible increase in arterial diameter by more than 50% relative to the normal vessel diameter. The incidence of aneurysm rupture is about 10 in 100 000 persons per year and ruptured arterial aneurysms inevitably results in serious complications, which are fatal in about 40% of cases. There is also a hereditary component of the disease and dilation of the ascending thoracic aorta is often associated with congenital heart disease such as bicuspid aortic valves (BAV). Furthermore, specific mutations that have been linked to aneurysm affect polymerization of actin filaments. Polymerization of actin is important to maintain a contractile phenotype of smooth muscle cells enabling these cells to resist mechanical stress on the vascular wall caused by the blood pressure according to the law of Laplace. Interestingly, polymerization of actin also promotes smooth muscle specific gene expression via the transcriptional co-activator MRTF, which is translocated to the nucleus when released from monomeric actin. In addition to genes encoding for proteins involved in the contractile machinery, recent studies have revealed that several non-coding microRNAs (miRNAs) are regulated by this mechanism. The importance of these miRNAs for aneurysm development is only beginning to be understood. This review will summarize our current understanding about the influence of smooth muscle miRNAs and actin polymerization for the development of arterial aneurysms.
  • References (65)
  • Citations (3)
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References65
Newest
Published on Sep 1, 2017in American Journal of Medical Genetics Part A 2.20
Thushiha Logeswaran2
Estimated H-index: 2
(University of Giessen),
Christoph Friedburg15
Estimated H-index: 15
(University of Giessen)
+ 10 AuthorsDietmar Schranz31
Estimated H-index: 31
(University of Giessen)
De novo heterozygous mutations changing R179 to histidine, leucine, or cysteine in the ACTA2 gene are associated with Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS). Characteristic hallmarks of this condition, caused only by these specific ACTA2 mutations, are congenital mydriasis (mid-dilated, non-reactive pupils), a large persistent ductus arteriosus (PDA), aortic aneurysms evolving during childhood, and cerebrovascular anomalies. We describe two patients, a 3-day-old newborn and a 2...
Zhenan Liu2
Estimated H-index: 2
(UTSW: University of Texas Southwestern Medical Center),
Audrey N. Chang12
Estimated H-index: 12
(UTSW: University of Texas Southwestern Medical Center)
+ 5 AuthorsEdward D. Korn56
Estimated H-index: 56
(NIH: National Institutes of Health)
The most common genetic alterations for familial thoracic aortic aneurysms and dissections (TAAD) are missense mutations in vascular smooth muscle (SM) α-actin encoded by ACTA2 . We focus here on ACTA2– R258C, a recurrent mutation associated with early onset of TAAD and occlusive moyamoya-like cerebrovascular disease. Recent biochemical results with SM α-actin–R258C predicted that this variant will compromise multiple actin-dependent functions in intact cells and tissues, but a model system to m...
Published on Jun 1, 2017in Biochimica et Biophysica Acta 3.79
Azra Alajbegovic5
Estimated H-index: 5
(Lund University),
Karolina M. Turczyńska8
Estimated H-index: 8
(Lund University)
+ 6 AuthorsSebastian Albinsson20
Estimated H-index: 20
(Lund University)
Abstract The dynamic properties of the actin cytoskeleton in smooth muscle cells play an important role in a number of cardiovascular disease states. The state of actin does not only mediate mechanical stability and contractile function but can also regulate gene expression via myocardin related transcription factors (MRTFs). These transcriptional co-activators regulate genes encoding contractile and cytoskeletal proteins in smooth muscle. Regulation of small non-coding microRNAs (miRNAs) by act...
Published on Jun 1, 2017in Heart and Vessels 1.62
Sebastian Albinsson20
Estimated H-index: 20
(Lund University),
Alessandro Della Corte29
Estimated H-index: 29
(Seconda Università degli Studi di Napoli)
+ 6 AuthorsAmalia Forte14
Estimated H-index: 14
(Seconda Università degli Studi di Napoli)
MicroRNAs are able to modulate gene expression in a range of diseases. We focused on microRNAs as potential contributors to the pathogenesis of ascending aorta (AA) dilatation in patients with stenotic tricuspid (TAV) or bicuspid aortic valve (BAV). Aortic specimens were collected from the ‘concavity’ and the ‘convexity’ of mildly dilated AAs and of normal AAs from heart transplant donors. Aortic RNA was analyzed through PCR arrays, profiling the expression of 84 microRNAs involved in cardiovasc...
Published on Jun 1, 2017in Heart Lung and Circulation 2.08
Jing Wu1
Estimated H-index: 1
,
Jun Wang2
Estimated H-index: 2
+ 3 AuthorsYunling Tian1
Estimated H-index: 1
(Lanzhou University)
Background MicroRNA-145 (miR-145) has been implicated in vascular smooth muscle cell differentiation, but the underlying mechanisms have not been fully understood, especially their role in abdominal aortic aneurysm (AAA) expansion. Here, we sought to explore and define the mechanisms of miR-145 function in the experimental AAA models in AngII-infused ApoE -/− mice. Methods miR-145 was overexpressed in ApoE -/− mice via lentivirus infection, and then the incidence of AAA, maximum abdominal aortic...
Published on Dec 1, 2016in BMC Medical Genetics 1.74
Tie Ke17
Estimated H-index: 17
(HUST: Huazhong University of Science and Technology),
Meng Han2
Estimated H-index: 2
(HUST: Huazhong University of Science and Technology)
+ 7 AuthorsTucheng Sun1
Estimated H-index: 1
(HUST: Huazhong University of Science and Technology)
Background Aortic aneurysms and/or dissection (AADs) in the aorta are a leading cause of human morbidity and mortality. To date, data on non-syndromic thoracic AADs (TAADs) have been mainly derived from Caucasians, and the genetic basis of TAADs remains to be elucidated. In this study, we assessed gene mutations in a Chinese population with TAADs.
Published on Oct 7, 2016in Journal of Biological Chemistry
Hailong Lu7
Estimated H-index: 7
(UVM: University of Vermont),
Patricia M. Fagnant12
Estimated H-index: 12
(UVM: University of Vermont)
+ 1 AuthorsKathleen M. Trybus45
Estimated H-index: 45
(UVM: University of Vermont)
Abstract Mutations in vascular smooth muscle α-actin (SM α-actin), encoded by ACTA2, are the most common cause of familial thoracic aortic aneurysms that lead to dissection (TAAD). The R179H mutation has a poor patient prognosis and is unique in causing multisystemic smooth muscle dysfunction (Milewicz, D. M., Ostergaard, J. R., Ala-Kokko, L. M., Khan, N., Grange, D. K., Mendoza-Londono, R., Bradley, T. J., Olney, A. H., Ades, L., Maher, J. F., Guo, D., Buja, L. M., Kim, D., Hyland, J. C., and R...
Published on Dec 1, 2015in Acta neuropathologica communications
Maria Magdalena Georgescu5
Estimated H-index: 5
(UTSW: University of Texas Southwestern Medical Center),
Marco C. Pinho12
Estimated H-index: 12
(UTSW: University of Texas Southwestern Medical Center)
+ 5 AuthorsDennis K. Burns52
Estimated H-index: 52
(UTSW: University of Texas Southwestern Medical Center)
Introduction Smooth muscle cell contraction is an essential function of arteries and relies on the integrity of the actin-myosin apparatus. The tissue-specific α2-smooth muscle actin, encoded by ACTA2, is predominantly expressed in vascular smooth muscle cells. ACTA2 mutations predispose to development of aortic aneurysms and early onset coronary and cerebrovascular disease. Based on arteriographic findings, a distinct cerebrovascular disease has been proposed for ACTA2 heterozygous patients car...
Published on Oct 27, 2015in Circulation 23.05
Gregory A. Roth48
Estimated H-index: 48
(UW: University of Washington),
Mark Daniel Huffman30
Estimated H-index: 30
(NU: Northwestern University)
+ 4 AuthorsChristopher Margono152
Estimated H-index: 152
(UW: University of Washington)
There is a global commitment to reduce premature cardiovascular diseases (CVDs) 25% by 2025. CVD mortality rates have declined dramatically over the past 2 decades, yet the number of life years lost to premature CVD deaths is increasing in low- and middle-income regions. Ischemic heart disease and stroke remain the leading causes of premature death in the world; however, there is wide regional variation in these patterns. Some regions, led by Central Asia, face particularly high rates of prematu...
Hailong Lu7
Estimated H-index: 7
(UVM: University of Vermont),
Patricia M. Fagnant12
Estimated H-index: 12
(UVM: University of Vermont)
+ 2 AuthorsKathleen M. Trybus45
Estimated H-index: 45
(UVM: University of Vermont)
Point mutations in vascular smooth muscle α-actin (SM α-actin), encoded by the gene ACTA2 , are the most prevalent cause of familial thoracic aortic aneurysms and dissections (TAAD). Here, we provide the first molecular characterization, to our knowledge, of the effect of the R258C mutation in SM α-actin, expressed with the baculovirus system. Smooth muscles are unique in that force generation requires both interaction of stable actin filaments with myosin and polymerization of actin in the subc...
Cited By3
Newest
Published on Jun 1, 2019in Journal of Cardiology 2.29
Silvia Pulignani5
Estimated H-index: 5
,
Andrea Borghini10
Estimated H-index: 10
,
Maria Grazia Andreassi37
Estimated H-index: 37
Abstract The risk of acute aortic events in patients with bicuspid aortic valve (BAV) constitutes a medical concern in terms of timing and surgical decision. During the past years, there has been a growing interest in the potential of microRNAs (miRNAs) as crucial epigenetic factors in multiple cellular processes associated with BAV aortopathy. Nevertheless, there are still challenges that need to be overcome before miRNAs could enter clinical practice, and further validation studies in larger a...
Published on Mar 1, 2019in Laboratory Investigation 3.68
Holly C. Williams6
Estimated H-index: 6
(Emory University),
Jing Ma3
Estimated H-index: 3
(Emory University)
+ 3 AuthorsAlejandra San Martin14
Estimated H-index: 14
(Emory University)
The dual specificity phosphatase slingshot homolog 1 (SSH1) contributes to actin remodeling by dephosphorylating and activating the actin-severing protein cofilin. The reorganization of the actin cytoskeleton has been implicated in chronic hypertension and the subsequent mechano-adaptive rearrangement of vessel wall components. Therefore, using a novel Ssh1−/− mouse model, we investigated the potential role of SSH1 in angiotensin II (Ang II)-induced hypertension, and vascular remodeling. We foun...
Published on Aug 1, 2018in Vascular Pharmacology 3.33
Kirsti Ytrehus28
Estimated H-index: 28
,
Jean-Sébastien Hulot43
Estimated H-index: 43
(Paris V: Paris Descartes University)
+ 2 AuthorsRosalinda Madonna24
Estimated H-index: 24
(University of Texas Health Science Center at Houston)
Abstract Perivascular fibrosis, the deposition of connective tissue around the vessels, has been demonstrated crucially involved in the development of cardiac dysfunction. Although cardiac fibrosis has been shown to be reversible under certain experimental conditions, effective anti-fibrotic therapies remain largely elusive. Therefore, perivascular fibrosis currently represents a major therapeutic target for cardiovascular diseases. The main topic of this review will be to address the mechanisms...
Published on Dec 7, 2017in Arteriosclerosis, Thrombosis, and Vascular Biology 6.62
Johan Holmberg20
Estimated H-index: 20
,
Anirban Bhattachariya6
Estimated H-index: 6
+ 9 AuthorsKarl Swärd25
Estimated H-index: 25
Objective— Pressure-induced myogenic tone is involved in autoregulation of local blood flow and confers protection against excessive pressure levels in small arteries and capillaries. Myogenic tone is dependent on smooth muscle microRNAs (miRNAs), but the identity of these miRNAs is unclear. Furthermore, the consequences of altered myogenic tone for hypertension-induced damage to small arteries are not well understood. Approach and Results— The importance of smooth muscle–enriched microRNAs, miR...