ijms-logo

Journal Browser

Journal Browser

Arteriogenesis—Molecular Regulation, Pathophysiology and Therapeutics II

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 45730

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

1. Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
2. Einthoven Laboratory for Experimental Vascular Medicine Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Interests: experimental vascular medicine; blood vessel; arteriogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will welcome original research articles and review papers on all molecular aspects of arteriogenesis. Potential topics include, but are not limited to, the following:

  • Genetic and Environmental Mechanisms Controlling Formation and Maintenance of the Native Collateral Circulation;
  • The Formation of Collateral Arterial Networks: Insights from the Developing Embryo;
  • Notch Signaling in Arteries: From Embryonic Development to Postnatal Homeostasis and Growth;
  • Multiple Pathways Converge in the Development of a Collateral Circulation (Arteriogenesis);
  • Fluid Shear Stress and its Pathways in Arteriogenesis;
  • The Impact of Shear Level and Cardiovascular Risk Factors on Bioavailable Nitric Oxide and Outward Vascular Remodeling in Mesenteric Arteries;
  • Epigenetic Mechanisms and Arteriogenesis;
  • Thymosin β4: A Promising Therapeutic Agent to Promote Arteriogenesis;
  • Bone Marrow Derived Cells in Arteriogenesis;
  • Local and Sustained Drug Delivery in Arteriogenesis;
  • Collateral Artery Growth in Man, from Assessment to Stimulation;
  • Stimulation of Arteriogenesis via External Counterpulsation.

PD Dr. Elisabeth Deindl
Prof. Dr. Paul Quax
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (12 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

3 pages, 153 KiB  
Editorial
From Increased Fluid Shear Stress to Natural Bypass Growth
by Elisabeth Deindl and Paul H. A. Quax
Int. J. Mol. Sci. 2020, 21(10), 3707; https://doi.org/10.3390/ijms21103707 - 25 May 2020
Viewed by 1475
Abstract
This Special Issue enqueues a series of publications dealing with arteriogenesis, which is the growth of a natural bypass from pre-existing arteriolar connections, as defined by Wolfgang Schaper, Werner Risau and Ramon Munoz-Chapuli in the late nineties of the last century [...] Full article

Research

Jump to: Editorial, Review

8 pages, 1273 KiB  
Communication
A Simple and Effective Flow Cytometry-Based Method for Identification and Quantification of Tissue Infiltrated Leukocyte Subpopulations in a Mouse Model of Peripheral Arterial Disease
by Konda Kumaraswami, Natallia Salei, Sebastian Beck, Stephan Rambichler, Anna-Kristina Kluever, Manuel Lasch, Lisa Richter, Barbara U. Schraml and Elisabeth Deindl
Int. J. Mol. Sci. 2020, 21(10), 3593; https://doi.org/10.3390/ijms21103593 - 19 May 2020
Cited by 7 | Viewed by 2927
Abstract
Arteriogenesis, the growth of a natural bypass from pre-existing arteriolar collaterals, is an endogenous mechanism to compensate for the loss of an artery. Mechanistically, this process relies on a locally and temporally restricted perivascular infiltration of leukocyte subpopulations, which mediate arteriogenesis by supplying [...] Read more.
Arteriogenesis, the growth of a natural bypass from pre-existing arteriolar collaterals, is an endogenous mechanism to compensate for the loss of an artery. Mechanistically, this process relies on a locally and temporally restricted perivascular infiltration of leukocyte subpopulations, which mediate arteriogenesis by supplying growth factors and cytokines. Currently, the state-of-the-art method to identify and quantify these leukocyte subpopulations in mouse models is immunohistology. However, this is a time consuming procedure. Here, we aimed to develop an optimized protocol to identify and quantify leukocyte subpopulations by means of flow cytometry in adductor muscles containing growing collateral arteries. For that purpose, adductor muscles of murine hindlimbs were isolated at day one and three after induction of arteriogenesis, enzymatically digested, and infiltrated leukocyte subpopulations were identified and quantified by flow cytometry, as exemplary shown for neutrophils and macrophages (defined as CD45+/CD11b+/Ly6G+ and CD45+/CD11b+/F4/80+ cells, respectively). In summary, we show that flow cytometry is a suitable method to identify and quantify leukocyte subpopulations in muscle tissue, and provide a detailed protocol. Flow cytometry constitutes a timesaving tool compared to histology, which might be used in addition for precise localization of leukocytes in tissue samples. Full article
Show Figures

Figure 1

11 pages, 2796 KiB  
Article
IL10 Alters Peri-Collateral Macrophage Polarization and Hind-Limb Reperfusion in Mice after Femoral Artery Ligation
by Alexander M. Götze, Christian Schubert, Georg Jung, Oliver Dörr, Christoph Liebetrau, Christian W. Hamm, Thomas Schmitz-Rixen, Christian Troidl and Kerstin Troidl
Int. J. Mol. Sci. 2020, 21(8), 2821; https://doi.org/10.3390/ijms21082821 - 17 Apr 2020
Cited by 8 | Viewed by 2235
Abstract
Arteriogenesis is a process by which a pre-existing arterioarterial anastomosis develops into a functional collateral network following an arterial occlusion. Alternatively activated macrophages polarized by IL10 have been described to promote collateral growth. This study investigates the effect of different levels of IL10 [...] Read more.
Arteriogenesis is a process by which a pre-existing arterioarterial anastomosis develops into a functional collateral network following an arterial occlusion. Alternatively activated macrophages polarized by IL10 have been described to promote collateral growth. This study investigates the effect of different levels of IL10 on hind-limb reperfusion and the distribution of perivascular macrophage activation types in mice after femoral artery ligation (FAL). IL10 and anti-IL10 were administered before FAL and the arteriogenic response was measured by Laser-Doppler-Imaging perioperatively, after 3, 7, and 14 d. Reperfusion recovery was accelerated when treated with IL10 and impaired with anti-IL10. Furthermore, symptoms of ischemia on ligated hind-limbs had the highest incidence after application of anti-IL10. Perivascular macrophages were immunohistologically phenotyped using CD163 and CD68 in adductor muscle segments. The proportion of alternatively activated macrophages (CD163+/CD68+) in relation to classically activated macrophages (CD163/CD68+) observed was the highest when treated with IL10 and suppressed with anti-IL10. This study underlines the proarteriogenic response with increased levels of IL10 and demonstrates an in-vivo alteration of macrophage activation types in the perivascular bed of growing collaterals. Full article
Show Figures

Figure 1

13 pages, 2164 KiB  
Communication
The Phosphatase SHP-2 Activates HIF-1α in Wounds In Vivo by Inhibition of 26S Proteasome Activity
by Yvonn Heun, Katharina Grundler Groterhorst, Kristin Pogoda, Bjoern F Kraemer, Alexander Pfeifer, Ulrich Pohl and Hanna Mannell
Int. J. Mol. Sci. 2019, 20(18), 4404; https://doi.org/10.3390/ijms20184404 - 07 Sep 2019
Cited by 10 | Viewed by 2714
Abstract
Vascular remodeling and angiogenesis are required to improve the perfusion of ischemic tissues. The hypoxic environment, induced by ischemia, is a potent stimulus for hypoxia inducible factor 1α (HIF-1α) upregulation and activation, which induce pro-angiogenic gene expression. We previously showed that the tyrosine [...] Read more.
Vascular remodeling and angiogenesis are required to improve the perfusion of ischemic tissues. The hypoxic environment, induced by ischemia, is a potent stimulus for hypoxia inducible factor 1α (HIF-1α) upregulation and activation, which induce pro-angiogenic gene expression. We previously showed that the tyrosine phosphatase SHP-2 drives hypoxia mediated HIF-1α upregulation via inhibition of the proteasomal pathway, resulting in revascularization of wounds in vivo. However, it is still unknown if SHP-2 mediates HIF-1α upregulation by affecting 26S proteasome activity and how the proteasome is regulated upon hypoxia. Using a reporter construct containing the oxygen-dependent degradation (ODD) domain of HIF-1α and a fluorogenic proteasome substrate in combination with SHP-2 mutant constructs, we show that SHP-2 inhibits the 26S proteasome activity in endothelial cells under hypoxic conditions in vitro via Src kinase/p38 mitogen-activated protein kinase (MAPK) signalling. Moreover, the simultaneous expression of constitutively active SHP-2 (E76A) and inactive SHP-2 (CS) in separate hypoxic wounds in the mice dorsal skin fold chamber by localized magnetic nanoparticle-assisted lentiviral transduction showed specific regulation of proteasome activity in vivo. Thus, we identified a new additional mechanism of SHP-2 mediated HIF-1α upregulation and proteasome activity, being functionally important for revascularization of wounds in vivo. SHP-2 may therefore constitute a potential novel therapeutic target for the induction of angiogenesis in ischemic vascular disease. Full article
Show Figures

Figure 1

12 pages, 1989 KiB  
Article
Development of an Exercise Training Protocol to Investigate Arteriogenesis in a Murine Model of Peripheral Artery Disease
by Ayko Bresler, Johanna Vogel, Daniel Niederer, Daphne Gray, Thomas Schmitz-Rixen and Kerstin Troidl
Int. J. Mol. Sci. 2019, 20(16), 3956; https://doi.org/10.3390/ijms20163956 - 14 Aug 2019
Cited by 9 | Viewed by 3104
Abstract
Exercise is a treatment option in peripheral artery disease (PAD) patients to improve their clinical trajectory, at least in part induced by collateral growth. The ligation of the femoral artery (FAL) in mice is an established model to induce arteriogenesis. We intended to [...] Read more.
Exercise is a treatment option in peripheral artery disease (PAD) patients to improve their clinical trajectory, at least in part induced by collateral growth. The ligation of the femoral artery (FAL) in mice is an established model to induce arteriogenesis. We intended to develop an animal model to stimulate collateral growth in mice through exercise. The training intensity assessment consisted of comparing two different training regimens in C57BL/6 mice, a treadmill implementing forced exercise and a free-to-access voluntary running wheel. The mice in the latter group covered a much greater distance than the former pre- and postoperatively. C57BL/6 mice and hypercholesterolemic ApoE-deficient (ApoE−/−) mice were subjected to FAL and had either access to a running wheel or were kept in motion-restricting cages (control) and hind limb perfusion was measured pre- and postoperatively at various times. Perfusion recovery in C57BL/6 mice was similar between the groups. In contrast, ApoE−/− mice showed significant differences between training and control 7 d postoperatively with a significant increase in pericollateral macrophages while the collateral diameter did not differ between training and control groups 21 d after surgery. ApoE−/− mice with running wheel training is a suitable model to simulate exercise induced collateral growth in PAD. This experimental set-up may provide a model for investigating molecular training effects. Full article
Show Figures

Figure 1

20 pages, 9444 KiB  
Article
Collateral Vessels Have Unique Endothelial and Smooth Muscle Cell Phenotypes
by Hua Zhang, Dan Chalothorn and James E Faber
Int. J. Mol. Sci. 2019, 20(15), 3608; https://doi.org/10.3390/ijms20153608 - 24 Jul 2019
Cited by 21 | Viewed by 5558
Abstract
Collaterals are unique blood vessels present in the microcirculation of most tissues that, by cross-connecting a small fraction of the outer branches of adjacent arterial trees, provide alternate routes of perfusion. However, collaterals are especially susceptible to rarefaction caused by aging, other vascular [...] Read more.
Collaterals are unique blood vessels present in the microcirculation of most tissues that, by cross-connecting a small fraction of the outer branches of adjacent arterial trees, provide alternate routes of perfusion. However, collaterals are especially susceptible to rarefaction caused by aging, other vascular risk factors, and mouse models of Alzheimer’s disease—a vulnerability attributed to the disturbed hemodynamic environment in the watershed regions where they reside. We examined the hypothesis that endothelial and smooth muscle cells (ECs and SMCs, respectively) of collaterals have specializations, distinct from those of similarly-sized nearby distal-most arterioles (DMAs) that maintain collateral integrity despite their continuous exposure to low and oscillatory/disturbed shear stress, high wall stress, and low blood oxygen. Examination of mouse brain revealed the following: Unlike the pro-inflammatory cobble-stoned morphology of ECs exposed to low/oscillatory shear stress elsewhere in the vasculature, collateral ECs are aligned with the vessel axis. Primary cilia, which sense shear stress, are present, unexpectedly, on ECs of collaterals and DMAs but are less abundant on collaterals. Unlike DMAs, collaterals are continuously invested with SMCs, have increased expression of Pycard, Ki67, Pdgfb, Angpt2, Dll4, Ephrinb2, and eNOS, and maintain expression of Klf2/4. Collaterals lack tortuosity when first formed during development, but tortuosity becomes evident within days after birth, progresses through middle age, and then declines—results consistent with the concept that collateral wall cells have a higher turnover rate than DMAs that favors proliferative senescence and collateral rarefaction. In conclusion, endothelial and SMCs of collaterals have morphologic and functional differences from those of nearby similarly sized arterioles. Future studies are required to determine if they represent specializations that counterbalance the disturbed hemodynamic, pro-inflammatory, and pro-proliferative environment in which collaterals reside and thus mitigate their risk factor-induced rarefaction. Full article
Show Figures

Figure 1

12 pages, 2064 KiB  
Communication
Insulin Treatment Forces Arteriogenesis in Diabetes Mellitus by Upregulation of the Early Growth Response-1 (Egr-1) Pathway in Mice
by Senthilkumar Thulasingam, Sundar Krishnasamy, David Raj C., Manuel Lasch, Srinivasan Vedantham and Elisabeth Deindl
Int. J. Mol. Sci. 2019, 20(13), 3320; https://doi.org/10.3390/ijms20133320 - 05 Jul 2019
Cited by 4 | Viewed by 2298
Abstract
The process of arteriogenesis is severely compromised in patients with diabetes mellitus (DM). Earlier studies have reported the importance of Egr-1 in promoting collateral outward remodeling. However, the role of Egr-1 in the presence of DM in outward vessel remodeling was not studied. [...] Read more.
The process of arteriogenesis is severely compromised in patients with diabetes mellitus (DM). Earlier studies have reported the importance of Egr-1 in promoting collateral outward remodeling. However, the role of Egr-1 in the presence of DM in outward vessel remodeling was not studied. We hypothesized that Egr-1 expression may be compromised in DM which may lead to impaired collateral vessel growth. Here, we investigated the relevance of the transcription factor Egr-1 for the process of collateral artery growth in diabetic mice. Induction of arteriogenesis by femoral artery ligation resulted in an increased expression of Egr-1 on mRNA and protein level but was severely compromised in streptozotocin-induced diabetic mice. Diabetes mellitus mice showed a significantly reduced expression of Egr-1 endothelial downstream genes Intercellular Adhesion Molecule-1 (ICAM-1) and urokinase Plasminogen Activator (uPA), relevant for extravasation of leukocytes which promote arteriogenesis. Fluorescent-activated cell sorting analyses confirmed reduced leukocyte recruitment. Diabetes mellitus mice showed a reduced expression of the proliferation marker Ki-67 in growing collaterals whose luminal diameters were also reduced. The Splicing Factor-1 (SF-1), which is critical for smooth muscle cell proliferation and phenotype switch, was found to be elevated in collaterals of DM mice. Treatment of DM mice with insulin normalized the expression of Egr-1 and its downstream targets and restored leukocyte recruitment. SF-1 expression and the diameter of growing collaterals were normalized by insulin treatment as well. In summary, our results showed that Egr-1 signaling was impaired in DM mice; however, it can be rescued by insulin treatment. Full article
Show Figures

Figure 1

17 pages, 2224 KiB  
Article
Effects on the Profile of Circulating miRNAs after Single Bouts of Resistance Training with and without Blood Flow Restriction—A Three-Arm, Randomized Crossover Trial
by Johanna Vogel, Daniel Niederer, Tobias Engeroff, Lutz Vogt, Christian Troidl, Thomas Schmitz-Rixen, Winfried Banzer and Kerstin Troidl
Int. J. Mol. Sci. 2019, 20(13), 3249; https://doi.org/10.3390/ijms20133249 - 02 Jul 2019
Cited by 19 | Viewed by 3906
Abstract
Background: The effects of blood flow restriction (training) may serve as a model of peripheral artery disease. In both conditions, circulating micro RNAs (miRNAs) are suggested to play a crucial role during exercise-induced arteriogenesis. We aimed to determine whether the profile of circulating [...] Read more.
Background: The effects of blood flow restriction (training) may serve as a model of peripheral artery disease. In both conditions, circulating micro RNAs (miRNAs) are suggested to play a crucial role during exercise-induced arteriogenesis. We aimed to determine whether the profile of circulating miRNAs is altered after acute resistance training during blood flow restriction (BFR) as compared with unrestricted low- and high-volume training, and we hypothesized that miRNA that are relevant for arteriogenesis are affected after resistance training. Methods: Eighteen healthy volunteers (aged 25 ± 2 years) were enrolled in this three-arm, randomized-balanced crossover study. The arms were single bouts of leg flexion/extension resistance training at (1) 70% of the individual single-repetition maximum (1RM), (2) at 30% of the 1RM, and (3) at 30% of the 1RM with BFR (artificially applied by a cuff at 300 mm Hg). Before the first exercise intervention, the individual 1RM (N) and the blood flow velocity (m/s) used to validate the BFR application were determined. During each training intervention, load-associated outcomes (fatigue, heart rate, and exhaustion) were monitored. Acute effects (circulating miRNAs, lactate) were determined using pre-and post-intervention measurements. Results: All training interventions increased lactate concentration and heart rate (p < 0.001). The high-intensity intervention (HI) resulted in a higher lactate concentration than both lower-intensity training protocols with BFR (LI-BFR) and without (LI) (LI, p = 0.003; 30% LI-BFR, p = 0.008). The level of miR-143-3p was down-regulated by LI-BFR, and miR-139-5p, miR-143-3p, miR-195-5p, miR-197-3p, miR-30a-5p, and miR-10b-5p were up-regulated after HI. The lactate concentration and miR-143-3p expression showed a significant positive linear correlation (p = 0.009, r = 0.52). A partial correlation (intervention partialized) showed a systematic impact of the type of training (LI-BFR vs. HI) on the association (r = 0.35 remaining after partialization of training type). Conclusions: The strong effects of LI-BFR and HI on lactate- and arteriogenesis-associated miRNA-143-3p in young and healthy athletes are consistent with an important role of this particular miRNA in metabolic processes during (here) artificial blood flow restriction. BFR may be able to mimic the occlusion of a larger artery which leads to increased collateral flow, and it may therefore serve as an external stimulus of arteriogenesis. Full article
Show Figures

Figure 1

Review

Jump to: Editorial, Research

17 pages, 926 KiB  
Review
The Extraordinary Role of Extracellular RNA in Arteriogenesis, the Growth of Collateral Arteries
by Anna-Kristina Kluever, Anna Braumandl, Silvia Fischer, Klaus T. Preissner and Elisabeth Deindl
Int. J. Mol. Sci. 2019, 20(24), 6177; https://doi.org/10.3390/ijms20246177 - 07 Dec 2019
Cited by 7 | Viewed by 2944
Abstract
Arteriogenesis is an intricate process in which increased shear stress in pre-existing arteriolar collaterals induces blood vessel expansion, mediated via endothelial cell activation, leukocyte recruitment and subsequent endothelial and smooth muscle cell proliferation. Extracellular RNA (eRNA), released from stressed cells or damaged tissue [...] Read more.
Arteriogenesis is an intricate process in which increased shear stress in pre-existing arteriolar collaterals induces blood vessel expansion, mediated via endothelial cell activation, leukocyte recruitment and subsequent endothelial and smooth muscle cell proliferation. Extracellular RNA (eRNA), released from stressed cells or damaged tissue under pathological conditions, has recently been discovered to be liberated from endothelial cells in response to increased shear stress and to promote collateral growth. Until now, eRNA has been shown to enhance coagulation and inflammation by inducing cytokine release, leukocyte recruitment, and endothelial permeability, the latter being mediated by vascular endothelial growth factor (VEGF) signaling. In the context of arteriogenesis, however, eRNA has emerged as a transmitter of shear stress into endothelial activation, mediating the sterile inflammatory process essential for collateral remodeling, whereby the stimulatory effects of eRNA on the VEGF signaling axis seem to be pivotal. In addition, eRNA might influence subsequent steps of the arteriogenesis cascade as well. This article provides a comprehensive overview of the beneficial effects of eRNA during arteriogenesis, laying the foundation for further exploration of the connection between the damaging and non-damaging effects of eRNA in the context of cardiovascular occlusive diseases and of sterile inflammation. Full article
Show Figures

Graphical abstract

20 pages, 4322 KiB  
Review
The Human Coronary Collateral Circulation, Its Extracardiac Anastomoses and Their Therapeutic Promotion
by Bigler Marius Reto and Christian Seiler
Int. J. Mol. Sci. 2019, 20(15), 3726; https://doi.org/10.3390/ijms20153726 - 30 Jul 2019
Cited by 25 | Viewed by 4992
Abstract
Cardiovascular disease remains the leading global cause of death, and the number of patients with coronary artery disease (CAD) and exhausted therapeutic options (i.e., percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical treatment) is on the rise. Therefore, the evaluation [...] Read more.
Cardiovascular disease remains the leading global cause of death, and the number of patients with coronary artery disease (CAD) and exhausted therapeutic options (i.e., percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical treatment) is on the rise. Therefore, the evaluation of new therapeutic approaches to offer an alternative treatment strategy for these patients is necessary. A promising research field is the promotion of the coronary collateral circulation, an arterio-arterial network able to prevent or reduce myocardial ischemia in CAD. This review summarizes the basic principles of the human coronary collateral circulation, its extracardiac anastomoses as well as the different therapeutic approaches, especially that of stimulating the extracardiac collateral circulation via permanent occlusion of the internal mammary arteries. Full article
Show Figures

Figure 1

14 pages, 666 KiB  
Review
Variations in Surgical Procedures for Inducing Hind Limb Ischemia in Mice and the Impact of These Variations on Neovascularization Assessment
by Zeen Aref, Margreet R. de Vries and Paul H.A. Quax
Int. J. Mol. Sci. 2019, 20(15), 3704; https://doi.org/10.3390/ijms20153704 - 29 Jul 2019
Cited by 38 | Viewed by 8595
Abstract
Mouse hind limb ischemia is the most common used preclinical model for peripheral arterial disease and critical limb ischemia. This model is used to investigate the mechanisms of neovascularization and to develop new therapeutic agents. The literature shows many variations in the model, [...] Read more.
Mouse hind limb ischemia is the most common used preclinical model for peripheral arterial disease and critical limb ischemia. This model is used to investigate the mechanisms of neovascularization and to develop new therapeutic agents. The literature shows many variations in the model, including the method of occlusion, the number of occlusions, and the position at which the occlusions are made to induce hind limb ischemia. Furthermore, predefined end points and the histopathological and radiological analysis vary. These differences hamper the correlation of results between different studies. In this review, variations in surgical methods of inducing hind limb ischemia in mice are described, and the consequences of these variations on perfusion restoration and vascular remodeling are discussed. This study aims at providing the reader with a comprehensive overview of the methods so far described, and proposing uniformity in research of hind limb ischemia in a mouse model. Full article
Show Figures

Graphical abstract

18 pages, 2287 KiB  
Review
Applications of Ultrasound to Stimulate Therapeutic Revascularization
by Catherine M. Gorick, John C. Chappell and Richard J. Price
Int. J. Mol. Sci. 2019, 20(12), 3081; https://doi.org/10.3390/ijms20123081 - 24 Jun 2019
Cited by 16 | Viewed by 4323
Abstract
Many pathological conditions are characterized or caused by the presence of an insufficient or aberrant local vasculature. Thus, therapeutic approaches aimed at modulating the caliber and/or density of the vasculature by controlling angiogenesis and arteriogenesis have been under development for many years. As [...] Read more.
Many pathological conditions are characterized or caused by the presence of an insufficient or aberrant local vasculature. Thus, therapeutic approaches aimed at modulating the caliber and/or density of the vasculature by controlling angiogenesis and arteriogenesis have been under development for many years. As our understanding of the underlying cellular and molecular mechanisms of these vascular growth processes continues to grow, so too do the available targets for therapeutic intervention. Nonetheless, the tools needed to implement such therapies have often had inherent weaknesses (i.e., invasiveness, expense, poor targeting, and control) that preclude successful outcomes. Approximately 20 years ago, the potential for using ultrasound as a new tool for therapeutically manipulating angiogenesis and arteriogenesis began to emerge. Indeed, the ability of ultrasound, especially when used in combination with contrast agent microbubbles, to mechanically manipulate the microvasculature has opened several doors for exploration. In turn, multiple studies on the influence of ultrasound-mediated bioeffects on vascular growth and the use of ultrasound for the targeted stimulation of blood vessel growth via drug and gene delivery have been performed and published over the years. In this review article, we first discuss the basic principles of therapeutic ultrasound for stimulating angiogenesis and arteriogenesis. We then follow this with a comprehensive cataloging of studies that have used ultrasound for stimulating revascularization to date. Finally, we offer a brief perspective on the future of such approaches, in the context of both further research development and possible clinical translation. Full article
Show Figures

Graphical abstract

Back to TopTop