Projects
Our general goal is to unravel the mechanisms behind the (patho)physiology of vascular remodeling, which we pursue through a broad scope of research topics and the use of state-of-the art imaging strategies.
Our general goal to………………………………………………………………………………………………………………………………………………………….
Intraplaque angiogenesis
Our group has a specific interest in studying intraplaque angiogenesis with a focus on endothelial cells and transendothelial migration. Intraplaque angiogenesis is associated with atherosclerotic plaque progression, since neovessels growing into the hypoxic plaque are often immature. As a result, these neovessels lack a proper barrier function rendering them susceptible to extravasation of leukocytes and erythrocytes. The murine model for vein graft atherosclerosis that we work with provides us an unique opportunity to study intraplaque angiogenesis, which is normally not seen in native murine atherosclerosis. We have demonstrated that interfering in the angiogenic pathway either pharmacologically or genetically can improve intraplaque angiogenesis which functionally leads to better outcomes in our murine model for vein graft atherosclerosis. Current projects with our (inter)national collaborators aim to target transendothelial migration to reduce cardiovascular disease burden.
Parma L, Baganha F et al. Eu J Pharmacol. 2017
Sier VQ, de Jong A, Quax PHA, de Vries MR. IJMS 2022
Ultrasound imaging of vascular remodeling and blood flow
Ultra-high frequency ultrasound imaging enables us to non-invasively quantify vascular remodeling and alterations in blood flow over time in murine arteriovenous fistula and vein graft models. We have shown that distinct blood flow patterns can be observed at specific sites while using clinically-relevant parameters. Structurally, we are capable to visualize and quantify changes in wall volume in three dimensions. Future studies will translate in vivo measurements to computermodels to further understand the interrelationship between blood flow patterns and structural remodeling on arteriovenous fistula and vein graft failure.
Photoacoustic imaging of plaque components
Photoacoustic imaging is a novel imaging modality than can achieve near optical resolution several centimeters deep for in vivo imaging. The mechanism of photoacoustics can simplistically described as “light in, sound out”. A pulsed laser is directed on the tissue and with an ultrasound transducer detects the acoustic waves. The technique lends itself for combination with ultrasound imaging and several components can be imaged using this technique. Tissue intrinsic components that have photoacoustic properties include hemoglobin, lipids and collagen. However, in our research group we are interested in more than these tissue intrinsic components. We are working in using targeted photoacoustic components as well, which we want to use to image different cells types, such as immune cells, endothelial cells and more. Using both tissue intrinsic and extrinsic targeted component we intend to imaging cardiovascular diseases in a novel way.
Trocha KM, Kip P. et al. Cardiovasc Res. 2020
Dietary restriction to improve (postoperative) vascular remodeling
Dietary restriction is an umbrella term encompassing a reduction in intake of total calories, proteins, specific amino acids (such as Methionine and Cysteine), or a combination of the aforementioned. Long-term dietary restriction has long been known to, extend both health and life span and decrease age-related disease in a wide variety of animal models as well as in humans. The beneficial effects of dietary restriction naturally also extend to cardiovascular health.
Our group has a specific interest in the use of protein as well as sulfur amino acid (Methionine) restriction as a means of a short-term pre-operative therapeutic intervention to beneficially modulate the mammalian response to surgical injury to improve outcomes of vascular surgery. Together with our international collaborators, we have demonstrated that short-term protein restriction improves outcomes of bypass surgery in our murine vein graft model. In addition, we have shown in both pre-clinical and clinical trials that various dietary restriction regimens are safe and ready for clinical testing. Current projects aim to delineate the relation between dietary restriction, perivascular adipose tissue, and microbiome to be ultimately used in a clinical setting to improve vascular remodeling.
The role of non-coding RNAs in vascular remodeling
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Cardiac Moonshot
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