Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice
Kip P, Sluiter TJ, MacArthur MR, Tao M, Kruit N, Mitchell SJ, Jung J, Kooijman S, Gorham J, Seidman JG, Quax PHA, Decano JL, Aikawa M, Ozaki CK, Mitchell JR and de Vries MR
Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice
Kip P, Sluiter TJ, MacArthur MR, Tao M, Kruit N, Mitchell SJ, Jung J, Kooijman S, Gorham J, Seidman JG, Quax PHA, Decano JL, Aikawa M, Ozaki CK, Mitchell JR and de Vries MR
Short-term preoperative methionine restriction (MetR) is a promising translatable strategy to mitigate surgical injury response. However, its application to improve post-interventional vascular remodeling remains underexplored. Here we find that MetR protects from arterial intimal hyperplasia in a focal stenosis model and pathologic vascular remodeling following vein graft surgery in male mice. RNA sequencing reveals that MetR enhances browning in arterial (thoracic aorta) perivascular adipose tissue (PVAT) and induces it in venous (caval vein) PVAT. Specifically, Ppara is highly upregulated in PVAT-adipocytes upon MetR. Furthermore, MetR dampens the postoperative pro-inflammatory response to surgery in PVAT-macrophages in vivo and in vitro. This study shows that the detrimental effects of dysfunctional PVAT on vascular remodeling can be reversed by MetR, and identifies pathways involved in MetR-induced browning of PVAT. Furthermore, we demonstrate the potential of short-term preoperative MetR as a simple intervention to ameliorate vascular remodeling after vascular surgery.
Hemodynamic considerations in arteriovenous vascular access modalities for hemodialysis
White NA, Xiao Z, DE Winter EP, Li M, DE Vries MR, VAN DER Bogt KE and Rotmans JI
Hemodynamic considerations in arteriovenous vascular access modalities for hemodialysis
White NA, Xiao Z, DE Winter EP, Li M, DE Vries MR, VAN DER Bogt KE and Rotmans JI
Arteriovenous fistulas and arteriovenous grafts are the most commonly used vascular access for hemodialysis in patients with end-stage chronic kidney disease. However, both methods face significant challenges due to the hemodynamic disturbances induced by the arteriovenous anastomosis. This causes changes in vascular structure and blood flow velocity near the anastomosis site after the fistula/graft surgery, and introduces abnormal wall shear stress and cyclic stretch. This leads to endothelial cell dysfunction, vascular smooth muscle cell proliferation, and adverse remodeling. The resulting effects include low patency rates due to vascular stenosis caused by intimal hyperplasia and insufficient outward remodeling. Additionally, the high flow conduit has been linked to adverse cardiac remodeling. To address this, various strategies have been explored to correct these localized hemodynamic abnormalities, aiming to improve long-term patency rates. In this review, an overview is provided of the current surgical techniques, anastomosis types, anastomosis angles, external scaffolds, modified fistula designs, and types of grafts. It evaluates the impact of these approaches on local hemodynamics in the access conduit and their potential effects on patient outcomes.
Imaging and Quantification of the Hepatic Vasculature of Mice Using Ultrafast Doppler Ultrasound
Stripling K, Timmermans F, Décombas-Deschamps S, Thalgott JH, Lemonnier D, de Vries MR, Rabelink TJ, Tanter M, Deffieux T and Lebrin F
Imaging and Quantification of the Hepatic Vasculature of Mice Using Ultrafast Doppler Ultrasound
Stripling K, Timmermans F, Décombas-Deschamps S, Thalgott JH, Lemonnier D, de Vries MR, Rabelink TJ, Tanter M, Deffieux T and Lebrin F
Non-invasive in vivo imaging of the vasculature is a powerful tool for studying disease mechanisms in rodents. To achieve high sensitivity imaging of the microvasculature using Doppler ultrasound methods, imaging modalities employing the concept of ultrafast imaging are preferred. By increasing the frame rate of the ultrasound scanner to thousands of frames per second, it becomes possible to improve the sensitivity of the blood flow down to 2 mm/s and to obtain functional information about the microcirculation in comparison to a sensitivity of around 1 cm/s in conventional Doppler modes. While Ultrafast Doppler ultrasound (UFUS) imaging has become adopted in neuroscience, where it can capture brain activity through neurovascular coupling, it presents greater challenges when imaging the vasculature of abdominal organs due to larger motions linked to breathing. The liver, positioned anatomically under the diaphragm, is particularly susceptible to out-of-plane movement and oscillating respiratory motion. These artifacts not only adversely affect Doppler imaging but also complicate the anatomical analysis of vascular structures and the computation of vascular parameters. Here, we present a qualitative and quantitative imaging analysis of the hepatic vasculature in mice by UFUS. We identify major anatomical vascular structures and provide graphical illustrations of the hepatic macroscopical anatomy, comparing it to an in-depth anatomical assessment of the hepatic vasculature based on Doppler readouts. Additionally, we have developed a quantification protocol for robust measurements of hepatic blood volume of the microvasculature over time. To contemplate further research, qualitative vascular analysis provides a comprehensive overview and suggests a standardized terminology for researchers working with mouse models of liver disease. Furthermore, it offers the opportunity to apply ultrasound as a non-invasive complementary method to inspect hepatic vascular defects in vivo and measure functional microvascular alterations deep within the organ before unraveling blood vessel anomalies at the micron scale levels using ex vivo staining on tissue sections.
Myeloid PHD2 Conditional Knockout Improves Intraplaque Angiogenesis and Vascular Remodeling in a Murine Model of Venous Bypass Grafting
Sluiter TJ, Tillie RJHA, de Jong A, de Bruijn JBG, Peters HAB, van de Leijgraaf R, Halawani R, Westmaas M, Starink LIW, Quax PHA, Sluimer JC and de Vries MR
Myeloid PHD2 Conditional Knockout Improves Intraplaque Angiogenesis and Vascular Remodeling in a Murine Model of Venous Bypass Grafting
Sluiter TJ, Tillie RJHA, de Jong A, de Bruijn JBG, Peters HAB, van de Leijgraaf R, Halawani R, Westmaas M, Starink LIW, Quax PHA, Sluimer JC and de Vries MR
Intraplaque angiogenesis occurs in response to atherosclerotic plaque hypoxia, which is driven mainly by highly metabolically active macrophages. Improving plaque oxygenation by increasing macrophage hypoxic signaling, thus stimulating intraplaque angiogenesis, could restore cellular function and neovessel maturation, and decrease plaque formation. Prolyl hydroxylases (PHDs) regulate cellular responses to hypoxia. We therefore aimed to elucidate the role of myeloid PHD2, the dominant PHD isoform, on intraplaque angiogenesis in a murine model for venous bypass grafting.
Basic Vascular Science 2024 Meeting
Sluiter TJ, Cruddas L, Ninno F, Schmitz-Rixen T, Tsui J and de Vries MR
Basic Vascular Science 2024 Meeting
Sluiter TJ, Cruddas L, Ninno F, Schmitz-Rixen T, Tsui J and de Vries MR
The Basic Vascular Science (BVS) meeting was set up to provide a forum for researchers and clinicians in the field to exchange knowledge and ideas and to foster cross-disciplinary collaborations. The BVS 2024 meeting was held in Berlin. Attended by vascular surgeons and physicians, interventional radiologists, basic science researchers, and engineers, the meeting continues to successfully attract both early career researchers and established clinician-scientists. Here, we report on the scientific sessions encompassing keynote lectures and oral presentations.
