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Anton-Jan van Zonneveld

Publications and source records attributed to Anton-Jan van Zonneveld.

7 recordsLinked to original sources
PubMed2006

Cytochrome P450 epoxygenase gene function in hypoxic pulmonary vasoconstriction and pulmonary vascular remodeling.

We assessed pulmonary cytochrome P450 (CYP) epoxygenase expression and activity during hypoxia and explored the effects of modulating epoxygenase activity on pulmonary hypertension. The acute hypoxic vasoconstrictor response was studied in Swiss Webster mice, who express CYP2C29 in their lungs. Animals were pretreated with vehicle, the epoxygenase inhibitor (N-methylsulfonyl-6-[2-propargyloxyphenyl] hexanamide) or an inhibitor of the soluble epoxide hydrolase. Whereas the epoxygenase inhibitor attenuated hypoxic pulmonary constriction (by 52%), the soluble epoxide hydrolase inhibitor enhanced the response (by 39%), indicating that CYP epoxygenase-derived epoxyeicosatrienoic acids elicit pulmonary vasoconstriction. Aerosol gene transfer of recombinant adenovirus containing the human CYP2C9 significantly elevated mean pulmonary artery pressure and total pulmonary resistance indices, both of which were sensitive to the inhibitor sulfaphenazole. The prolonged exposure of mice to hypoxia increased CYP2C29 expression, and transcript levels increased 5-fold after exposure to normobaric hypoxia (FIO2 0.07) for 2 hours. This was followed by a 2-fold increase in protein expression and by a significant increase in epoxyeicosatrienoic acid production after 24 hours. Chronic hypoxia (7 days) elicited pulmonary hypertension and pulmonary vascular remodeling, effects that were significantly attenuated in animals continually treated with N-methylsulfonyl-6-[2-propargyloxyphenyl] hexanamide (-46% and -55%, respectively). Our results indicate that endogenously generated epoxygenase products are associated with hypoxic pulmonary hypertension in mice and that selective epoxygenase inhibition significantly reduces acute hypoxic pulmonary vasoconstriction and chronic hypoxia-induced pulmonary vascular remodeling. These observations indicate potential novel targets for the treatment of pulmonary hypertension and highlight a pivotal role for CYP epoxygenases in pulmonary responses to hypoxia.

Adenoviridae↗
PubMed2006

Endothelial progenitor cells: biology and therapeutic potential in hypertension.

PURPOSE OF REVIEW: In this review, we summarize some of the recent advances in our understanding of the biology of endothelial progenitor cells, and discuss the potential relevance of these progenitor cells for endothelial function and associated microvascular abnormalities that can form the structural basis of essential hypertension. RECENT FINDINGS: Both in experimental models of hypertension and in patients with hypertension, the function of endothelial progenitor cells is impaired. Also, some antihypertensive drugs that have been associated with reversal of endothelial function and microvascular rarefaction appear to correct endothelial progenitor cell dysfunction. SUMMARY: While information on endothelial progenitor biology is still limited in patients with hypertension in comparison with, for example, patients with coronary artery disease, it is a topic that warrants the attention of researchers in the hypertension field, as it may have important implications for the development of organ damage, and potentially could be linked to the pathogenesis of hypertension itself.

Antihypertensive Agents↗
PubMed2004

Endothelial progenitor cells: more than an inflammatory response?

The formation of new capillaries (angiogenesis) may be of clinical importance in facilitating reperfusion and regeneration of hibernating cardiac tissue after myocardial infarction and in microvascular ischemia. Evidence is accumulating that as part of the response to hypoxia, bone marrow-derived circulating endothelial progenitor cells (CEPs) are mobilized and subsequently differentiate into proper endothelial cells. There are also indications that such CEPs can facilitate endothelial repair and angiogenesis in vivo. It is not clear yet, however, whether these CEPs are essential for these adaptive processes or what the relative contribution of CEP is compared with that of other mononuclear inflammatory cells that are mobilized to areas of ischemia. Moreover, there are still many uncertainties about how cardiovascular risk factors alter CEP function. Particularly when therapeutically mobilizing CEPs, a further understanding of this issue is essential to assess the risk of potentially harmful side effects of altered CEP function.

Animals↗
PubMed2004

Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes.

Type 1 diabetes is associated with reduced vascular repair, as indicated by impaired wound healing and reduced collateral formation in ischemia. Recently, endothelial progenitor cells (EPCs) have been identified as important regulators of these processes. We therefore explored the concept that EPCs are dysfunctional in diabetes. The number of EPCs obtained from type 1 diabetic patients in culture was 44% lower compared with age- and sex-matched control subjects (P < 0.001). This reduction was inversely related to levels of HbA(1c) (R = -0.68, P = 0.01). In addition, we demonstrated that patient EPCs were also impaired in function using an in vitro angiogenesis assay. Conditioned media from patient EPCs were significantly reduced in their capacity to support endothelial tube formation in comparison to control EPCs. Therefore, despite culturing the EPCs under normoglycemic conditions, functional differences between patient and control EPCs were maintained. Our findings demonstrate that adverse metabolic stress factors in type 1 diabetes are associated with reduced EPC numbers and angiogenicity. We hypothesize that EPC dysfunction contributes to the pathogenesis of vascular complications in type 1 diabetes.

Adult↗
PubMed2002

Anti-inflammatory effects of tetrahydrobiopterin on early rejection in renal allografts: modulation of inducible nitric oxide synthase.

Oxidative stress contributes to the development of early transplant failure. As nitric oxide synthases (NOS) can act as sources of superoxide, we investigated the effect of the NOS cofactor tetrahydrobiopterin (BH4) on oxyradical production and early rejection in a rat kidney transplantation model. Allograft transplantation (Brown Norway to Lewis) showed more renal superoxide production and monocyte infiltration when compared with isografts (Lewis to Lewis). Administration of the stable BH4 precursor sepiapterin had no effect on superoxide production in the isografts (51+/-10 vs. 69+/-17 cps/10 mg protein), but led to a marked decrease in superoxide production in the allografts (116+/-11 vs. 60+/-6 cps/10 mg protein; P<0.05) and was accompanied by a reduction in periarterial macrophage infiltration (3.3+/-0.7 vs. 1.3+/-0.3 cells/vessel; P<0.05) and an increase in NO production (78+/-22 vs. 173+/-12 AU/g kidney) (P<0.01). In vitro experiments confirm that iNOS can produce superoxide mainly from the heme domain, whereas BH4 administration can reverse this superoxide production in the presence of adequate anti-oxidant defense. Our findings support the hypothesis that BH4 can be used to modulate the function of the inflammatory iNOS isoform and suggest a potential therapeutic role for sepiapterin in early allograft rejection.

Animals↗
PubMedDate not supplied

A study of neovascularization in the rat ischemic hindlimb using Araldite casting and Spalteholtz tissue clearing.

INTRODUCTION: Understanding neovascularization is an important prerequisite for therapeutic advances aimed at the salvation of ischemic tissues. We explored an alternative strategy to corrosion casting for visualizing neovascularization in a rat hindlimb ischemia model. METHODS: Rats were subjected to hindlimb ischemia by femoral artery ligation. Directly after femoral artery occlusion and at 7, 14, 21 and 28 days postsurgery, rats were sacrificed, and neovascularization was evaluated by vascular casting with Araldite plastic and subsequent Spalteholtz tissue clearing. RESULTS: Semitransparent preparations were obtained, in which the casted arteries could be directly and three-dimensionally visualized in detail and in relation to the surrounding tissue. In the vascular casts, collateral formation and recanalization of previously thrombosed arteries were demonstrated. CONCLUSIONS: We describe an alternative approach to study neovascularization in animal models. This method, which combines Araldite plastic vascular casting with Spalteholtz tissue clearing, preserves all vasculature as well as the surrounding tissue. In a small time series in rat ischemic hindlimbs, we show that restoration of blood flow after ischemia not only involves newly formed collaterals, but also recanalization of previously thrombosed arterial segments.

Animals↗