Statins Prevent the Deleterious Consequences of Placental Chemerin Upregulation in Preeclampsia.

Background: Chemerin, an inflammatory adipokine, is upregulated in preeclampsia, and its placental overexpression results in preeclampsia-like symptoms in mice. Statins may lower chemerin.

Methods: Chemerin was determined in a prospective cohort study in women suspected of preeclampsia and evaluated as a predictor versus the sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio.

Prospective evaluation of clinical outcomes between pre-cut corneal grafts prepared using a manual or automated technique: with one-year follow-up.

Purpose: Posterior lamellar corneal surgery is considered the standard of care for irreversible endothelial cell dysfunction. Pre-cut grafts can be prepared either manually (Descemet stripping endothelial keratoplasty; DSEK) or mechanically (Descemet stripping automated endothelial keratoplasty; DSAEK). We performed a head-to-head clinical comparison between DSEK and DSAEK grafts.

Qualitative evaluation of coronary atherosclerosis in a large cohort of young and middle-aged Dutch tissue donors implies that coronary thrombo-embolic manifestations are stochastic.

Background And Aims: With the intention to gain support for the hypothesis that incident ischemic complications of atherosclerotic disease involve a stochastic aspect, we performed a histological, qualitative evaluation of the epidemiology of coronary atherosclerotic disease in a cohort of aortic valve donors.

Patients And Methods: Donors (n = 695, median age 54, range 11-65 years) were dichotomized into a non-cardiovascular (non-CVD) and a cardiovascular disease death (CVD) group. Consecutive 5 mm proximal left coronary artery segments were Movat stained, and the atherosclerotic burden for each segment was graded (revised AHA-classification).

Sheep-Specific Immunohistochemical Panel for the Evaluation of Regenerative and Inflammatory Processes in Tissue-Engineered Heart Valves.

The creation of living heart valve replacements via tissue engineering is actively being pursued by many research groups. Numerous strategies have been described, aimed either at culturing autologous living valves in a bioreactor () or inducing endogenous regeneration by the host via resorbable scaffolds (). Whereas a lot of effort is being invested in the optimization of heart valve scaffold parameters and culturing conditions, the pathophysiological remodeling processes to which tissue-engineered heart valves are subjected upon implantation have been largely under-investigated.

High proportion of genetic cases in patients with advanced cardiomyopathy including a novel homozygous Plakophilin 2-gene mutation.

Cardiomyopathies might lead to end-stage heart disease with the requirement of drastic treatments like bridging up to transplant or heart transplantation. A not precisely known proportion of these diseases are genetically determined. We genotyped 43 index-patients (30 DCM, 10 ARVC, 3 RCM) with advanced or end stage cardiomyopathy using a gene panel which covered 46 known cardiomyopathy disease genes.

Histological evaluation disqualifies IMT and calcification scores as surrogates for grading coronary and aortic atherosclerosis.

Background/objectives: Carotid intimal media thickness (IMT) and coronary calcium scores (CCS) are thought to reflect atherosclerotic burden. The validity of this assumption for IMT is challenged by recent meta-analyses; for CCS by absence of a relationship between negative scores, and freedom of future events. As such, we considered evaluation of the relationship between tissue IMT and CCS, and extend of atherosclerotic disease relevant.

Age-Dependent Changes in Geometry, Tissue Composition and Mechanical Properties of Fetal to Adult Cryopreserved Human Heart Valves.

There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years) were analyzed.

Dihydroergotamine and sumatriptan in isolated human coronary artery, middle meningeal artery and saphenous vein.

Background: Dihydroergotamine (DHE) and sumatriptan are contraindicated in patients with cardiovascular disease because of their vasoconstricting properties, which have originally been explored in proximal coronary arteries. Our aim was to investigate DHE and sumatriptan in the proximal and distal coronary artery, middle meningeal artery and saphenous vein.

Methods: Blood vessel segments were mounted in organ baths and concentration response curves for DHE and sumatriptan were constructed.

Long-lasting physiological antagonism of calcitonin gene-related peptide towards endothelin-1 in rat mesenteric arteries and human coronary arteries.

Endothelin-1 causes long-lasting contraction via endothelin type A receptor (ETAR) in isolated rat mesenteric arteries (RMA) that cannot be readily terminated by removing the agonist, or by adding the ETAR antagonist BQ123 or the NO donor sodium nitroprusside. It could be terminated by adding calcitonin-gene related peptide (CGRP), most likely because CGRP causes ET-1/ETAR dissociation. Here we investigated this phenomenon in human coronary microarteries (HCMA).

Genetic variation and gender determine bradykinin type 1 receptor responses in human tissue: implications for the ACE-inhibitor-induced effects in patients with coronary artery disease.

The efficacy of the ACE (angiotensin-converting enzyme) inhibitor perindopril in coronary artery disease [EUROPA (European trial on reduction of cardiac events with perindopril in stable coronary artery disease) study] is associated with the rs12050217 A/G single nucleotide polymorphism in the B1 receptor (bradykinin type 1 receptor) gene. To investigate the underlying mechanism, we examined the effect of this polymorphism on B1-receptor-mediated coronary artery dilation and peripheral blood mononuclear cell activation. Vasorelaxant responses of human coronary microarteries from subjects without coronary disease to des-Arg(9)-bradykinin and to bradykinin were studied in organ bath experiments.

Compound 21 induces vasorelaxation via an endothelium- and angiotensin II type 2 receptor-independent mechanism.

Angiotensin II type 2 (AT(2)) receptor stimulation has been linked to vasodilation. Yet, AT(2) receptor-independent hypertension and hypotension (or no effect on blood pressure) have been observed in vivo after application of the AT(2) receptor agonist compound 21 (C21). We, therefore, studied its effects in vitro, using preparations known to display AT(2) receptor-mediated responses.

Angiotensin II-aldosterone interaction in human coronary microarteries involves GPR30, EGFR, and endothelial NO synthase.

Aims: The aim of this study was to investigate the aldosterone-angiotensin (Ang) II interaction in human coronary microarteries (HCMAs).

Methods And Results: HCMAs, obtained from 75 heart-beating organ donors, were mounted in myographs and exposed to Ang II, either directly or following a 30-min pre-incubation with aldosterone, 17β-oestradiol, hydrocortisone, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, the extracellular regulated kinase 1/2 (ERK1/2) inhibitor PD98059, the GPR30 antagonist G15, or the epidermal growth factor receptor (EGFR) antagonist AG1478. Ang II constricted HCMAs in a concentration-dependent manner.

Pharmacological characterization of VIP and PACAP receptors in the human meningeal and coronary artery.

Objective: We pharmacologically characterized pituitary adenylate cyclase-activating polypeptides (PACAPs), vasoactive intestinal peptide (VIP) and the VPAC(1), VPAC(2) and PAC(1) receptors in human meningeal (for their role in migraine) and coronary (for potential side effects) arteries.

Methods: Concentration response curves to PACAP38, PACAP27, VIP and the VPAC(1) receptor agonist ([Lys15,Arg16,Leu27]-VIP[1-7]-GRF[8-27]) were constructed in the absence or presence of the PAC(1) receptor antagonist PACAP6-38 or the VPAC(1) receptor antagonist, PG97269. mRNA expression was measured using qPCR.

Steroidogenesis vs. steroid uptake in the heart: do corticosteroids mediate effects via cardiac mineralocorticoid receptors?

Objective: To test whether glucocorticoids act as the endogenous agonist of cardiac mineralocorticoid receptors, we evaluated the cardiac effects of aldosterone and corticosterone and cardiac steroidogenesis vs. steroid uptake from plasma.

Methods And Results: Both corticosterone and aldosterone increased left ventricular pressure in the rat heart.

Functional characterization of contractions to tegaserod in human isolated proximal and distal coronary arteries.

Tegaserod, a 5-HT(4) receptor agonist, has been used to treat idiopathic constipation and constipation-predominant irritable bowel disease. It has recently been suggested that tegaserod has an affinity for 5-HT(1B) receptors, which mediate vasoconstriction. As some patients have experienced cardiac ischemia during treatment with tegaserod, we assessed contractions to tegaserod in healthy and diseased human isolated coronary arteries and compared the results with those obtained using sumatriptan, an established 5-HT(1B) receptor agonist.

Collagen cross-linking by adipose-derived mesenchymal stromal cells and scar-derived mesenchymal cells: Are mesenchymal stromal cells involved in scar formation?

In this work, different fibroblast-like (mesenchymal) cell populations that might be involved in wound healing were characterized and their involvement in scar formation was studied by determining collagen synthesis and processing. Depending on the physical and mechanical properties of the tissues, specific collagen cross-linking routes are followed. In skin the cross-linking of the pyridinium type is normally very low; however, in different forms of fibrosis increased levels of this type of cross-linking have been found.

Development of an in vitro burn wound model.

Healing of a deeper burn wound is a complex process that often leads to scar formation. Skin wound model systems are important for the development of treatments preventing scarring. The aim of this study is to develop a standardized in vitro burn wound model that resembles the in vivo situation.

Culture of keratinocytes for transplantation without the need of feeder layer cells.

Patients with large burn wounds have a limited amount of healthy donor skin. An alternative for the autologous skin graft is transplantation with autologous keratinocytes. Conventionally, the keratinocytes are cultured with mouse feeder layer cells in medium containing fetal calf serum (FCS) to obtain sufficient numbers of cells.

Expression profile of proteins involved in scar formation in the healing process of full-thickness excisional wounds in the porcine model.

Scar formation in deep dermal wounds is associated with excessive collagen deposition and contraction. Increased collagen synthesis and decreased collagen degradation are the mechanisms through which this form of fibrosis can occur. Another factor might be a different kind of collagen cross-linking seen in fibrotic skin diseases.

Culture of Keratinocytes for Transplantation without the Need of Feeder Layer Cells.

Patients with large burn wounds have a limited amount of healthy donor skin. An alternative for the autologous skin graft is transplantation with autologous keratinocytes. Conventionally, the keratinocytes are cultured with mouse feeder layer cells in medium containing fetal calf serum (FCS) to obtain sufficient numbers of cells.

Increased formation of pyridinoline cross-links due to higher telopeptide lysyl hydroxylase levels is a general fibrotic phenomenon.

Fibrosis is characterized by an excessive accumulation of collagen which contains increased levels of pyridinoline cross-links. The occurrence of pyridinolines in the matrix is an important criterion in assessing the irreversibility of fibrosis, which suggests that collagen containing pyridinoline cross-links significantly contributes to the unwanted collagen accumulation. Pyridinoline cross-links are derived from hydroxylated lysine residues located within the collagen telopeptides (hydroxyallysine pathway).

Upside-down transfer of porcine keratinocytes from a porous, synthetic dressing to experimental full-thickness wounds.

Currently, the use of cultured epithelial autografts as an alternative to split-thickness skin autografts for coverage of full-thickness wounds is limited due to fragility of the sheet and variability in the outcome of healing. This could be circumvented by the transfer of proliferating keratinocytes, instead of differentiated sheets, to the wound bed and the "in vivo" regeneration of epidermis. The aim of this study was to achieve re-epithelialization on experimental full-thickness wounds in the pig using a porous, synthetic carrier seeded with proliferating keratinocytes.

Differential expression of CRABP-II in fibroblasts derived from dermis and subcutaneous fat.

We have shown previously that fibroblasts derived from fat or dermal tissue differ in their functional properties, such as proliferation rate and contractile properties. To study these differences further, two-dimensional electrophoresis (2D PAGE) was performed on proteins isolated from cultured subcutaneous fat and dermal fibroblasts. The 2D gels were screened for proteins that were differentially expressed in all donors (n = 5).