Biology of Vascular Diseases

Current treatments involve replacement of the aorta. With more knowledge of the disease process, however, scientists may learn how to prevent the problem altogether. Much research has been dedicated to describing the exact changes within our arteries that result in atherosclerosis and aneurysm. Looking forward, research will focus on understanding:.

Vascular biology research can lead to the prevention of the diseases that are the leading causes of death in Western cultures, including heart attack and stroke. This research is very costly to perform but can lead to significant improvement in lifespan and quality of life.

MicroRNAs in Vascular Biology and Vascular Disease

Most medical research is supported by government, the health care industry and various foundations, including the Society for Vascular Surgery Foundation. Contributions from patients are critical to the advancement of vascular biology and all of its benefits. Donate to the SVS Foundation. We are a not-for-profit professional medical society, composed primarily of vascular surgeons, that seeks to advance excellence and innovation in vascular health through education, advocacy, research, and public awareness.

Skip to main content. Patient Resources What is a Vascular Surgeon? What is a Vascular Surgeon? Blood vessels are composed of three layers. The inner layer intima is lined by specialized cells called endothelial cells. One of the main functions of this lining is to keep the vessels from clotting. The middle layer media is composed of muscle cells, and allows the vessels to expand and contract. The outer layer adventitia provides strength so vessels do not burst under pressure. When these arteries become diseased, a stroke brain damage may result.

When the wall of the aorta weakens, it starts to dilate. Rupture of the aorta in this circumstance can lead to death. What scientists hope to learn Scientists hope to learn effective methods for preventing leading vascular diseases like atherosclerosis. It is well established that neointimal formation is resulted from EC injury and activation followed by white blood cell infiltration, lipid deposition, and VSMC dedifferentiation, proliferation, and migration in the vascular walls.

Using microarray analysis, these investigators demonstrated that miRNAs were highly expressed in normal rat arteries. Interestingly, in vascular walls with neointimal growth induced by balloon-catheter angioplasty, many of the detected miRNAs are aberrantly expressed [ 13 ]. The broadly deregulated miRNAs in injured arteries indicated that multiple miRNAs are involved in vascular injury responses that match the complex feature of neointimal growth in diverse vascular diseases in which multiple genes participated.

The aberrant expression of miRNA was not limited to rat model. In mouse arteries with neointimal growth after ligation injury, both miR and miR were downregulated as reported by Cordes et al. Moreover, in atherosclerotic human and mouse arteries without mechanical injuries, some of miRNAs were also deregulated as demonstrated in recent reports by Elia et al. Table 2 shows the miRNAs that are highly expressed in vascular walls and are aberrantly expressed in animal and human arteries with neointimal lesion formation.

The putative cellular functions of these miRNAs are also listed Table 2. Aberrantly expressed miRNAs in diseased vascular walls and their potential cellular functions. VSMC dedifferentiation, migration, proliferation, and apoptosis are critical cellular events responsible for the development of a number of proliferative vascular diseases. Indeed, VSMCs are the major cells within neointimal lesions in these vascular diseases. We demonstrated that miR, a miRNA that is upregulated in vascular walls with neointima, was a critical regulator for VSMC proliferation and apoptosis [ 13 ].

In contrast, VSMC proliferation was decreased, but apoptosis was increased via miR inhibition through its inhibitor. More recently, the roles of miR and miR in VSMC biology have received special attention because they are abundant miRNAs in normal vascular walls and their expression is downregulated in diseased arteries [ 13 , 15 , 31 — 33 , 36 , 37 ]. We identified that miR was selectively expressed in VSMCs of arterial walls and its expression was significantly downregulated in differentiated, proliferative VSMCs [ 15 ].

You are here

Both in cultured cells in vitro and in balloon-injured rat carotid arteries in vivo, we demonstrated that miR was a novel biomarker and a critical modulator for VSMC phenotype [ 15 ]. Moreover, the expression of VSMC differentiation maker genes was significantly upregulated by overexpression of miR, but was downregulated by miR inhibition. To determine the potential gene targets of miR in VSMCs, both bioinformatic and experimental approaches were applied.

However, in contrast to the inhibitory effect of a miRNA on its target genes, overexpression of miR increased the expression of myocardin. However, our explanation was that at least in part, the upregulated myocardin is induced by an indirect effect of miR through its target gene KLF5 [ 15 ].

If myocardin is indeed a direct target of miR but the expression is increased by miR, it could be a new discovery because recent studies revealed that some small RNAs may be able to increase their target gene expression via RNA activation mechanisms RNAa [ 38 ]. In addition to the above studies, Boettger et al.

• Senza ritorno (Italian Edition)?
• Jin Shin Fee?
• The Lady from Santa Fe?
• Everest and Conquest in the Himalaya: Science and Courage on the World’s Highest Mountain?
• Writing Pill 9: Im almost done in. I need to spell. (Royce Levi’s 20 Writing Pills to cure your English illnesses.);
• Allure Book 2 State Of Romance (Contemporary Romance)!
• Pathophysiology of CVD in diabetes?

More excitedly, miR was found to play a critical role in keeping the contractive functions of VSMCs and vessels [ 36 ], which matched our finding regarding the role of miR in VSMC phenotype. Regulation of vascular smooth muscle cell functions by miR and miR These targets are able to regulate VSMC cell differentiation, proliferation, and contraction directly or indirectly via interaction with serum response factor SRF.

The effects of miRNAs on vascular disease have recently been intensively explored [ 13 — 15 , 36 — 38 , 42 ].

In addition, the neointimal formation in carotid arteries was also significantly reduced by restoration of miR after angioplasty [ 15 ]. The negative effect of miR on vascular neointimal growth was also demonstrated in another study using the same rat model [ 33 ]. However, Xin et al. Obviously the result was different from that obtained in Dr. Braun's study [ 36 ] and also different from our unpublished data in mouse carotid artery guide-wire injury and air drying injury models using the pharmacological approaches. The mechanism for the different results is unclear. We think it might be related to the following reasons: Second, neointimal formation in ligation model is dependent on the distance to the ligation site, which is difficult for the correct histological analysis.

In addition, the neointimal response in carotid artery ligation model often has big difference even among the same group. Other injury models such as air dying injury and guide-wire injury guide-wire injury should be performed in ApoE mice should be tested in these knockout mice. More recently, Zernecke et al. Genetic variations of pre-miRNAs, mature miRNAs, and their target genes determined by gene polymorphisms and single-nucleotide polymorphisms have revealed that the variations of pre-miRNAs, mature miRNAs, and miRNA binding sites in their target genes are related to many human diseases such as cancer and heart disease [ 43 — 45 ].

More polymorphism studies on miRNAs and their targets involved in vascular diseases should be performed. Unlike cancer tissues, human vessel tissues with vascular diseases are not easy to be obtained. However, exciting results from animal studies have revealed that many critical genes related to vascular diseases are regulated by miRNAs.

Some miRNAs have strong effects on vascular cell functions and vascular lesions in animals. Limited human atherosclerotic studies have also revealed that multiple miRNAs are deregulated [ 32 , 33 ]. Clearly, more clinical studies should be performed using human vessel tissues.

Vascular disease

In addition, human miRNA studies using blood cells isolated from patients with vascular diseases could be an alternative approach for the clinical studies in this area. The initial exciting results have demonstrated that multiple miRNAs are involved in the development of both human and animal vascular diseases via regulating vascular cell differentiation, migration, proliferation, and apoptosis through their target genes. Several in vivo animal studies have revealed the promising therapeutic results in vascular disease. Thus, miRNAs may represent new biomarkers and therapeutic targets for diverse vascular diseases.

As we know well, the vascular diseases are multifactorial complex diseases in which many genes are involved. On the other hand, multiple target genes might induce some unexpected side effects, and this could be the disadvantage [ 47 ]. However, as miRNAs are endogenous, restoration of the aberrantly expressed miRNAs to the physiological levels should not have major unexpected side effects. We should realize that we are still at the early stages in miRNA-based therapy.

Vascular Biology | Society for Vascular Surgery

The following studies should be performed before it can be used in the clinic. First, the critical miRNAs responsible for the development of vascular diseases should be further identified. Second, the detailed cellular and molecular mechanisms of these critical miRNAs in the prevention and treatment of vascular diseases should be studied. Fourth, although methods are available to downregulate miRNA in vivo, technology for upregulating miRNA in the vascular walls in vivo requires development.

Finally, the potential side effects of miRNA-based therapy should be studied before application in the clinic. National Center for Biotechnology Information , U. J Cardiovasc Transl Res. Author manuscript; available in PMC Apr Author information Copyright and License information Disclaimer.

Society for Vascular Surgery

The publisher's final edited version of this article is available at J Cardiovasc Transl Res. See other articles in PMC that cite the published article. Table 1 Angiogenesis-related miRNAs and their target genes. Open in a separate window. Table 2 Aberrantly expressed miRNAs in diseased vascular walls and their potential cellular functions.

Conclusion and Perspective miRNAs in vascular biology and vascular disease has emerged as a new research area. The functions of animal microRNAs. Posttranscriptional regulation of the heterochronic gene lin by lin-4 mediates temporal pattern formation in C.

• Vascular disease - Wikipedia!
• A Voyage Around the World in 1766- 1769, with charts.
• Our Daily Bread (Tales of the Gray Prince Book 2).
• Navigation menu?
• Introduction;
• MicroRNAs in vascular biology and vascular disease..
• A Mushroom in the Bathroom (Amarys and Indigo Book 1).

Identification of novel genes coding for small expressed RNAs. Critical mediators of differentiation, development and disease. Identification of hundreds of conserved and nonconserved human microRNAs. Chen K, Rajewsky N.