Biomedical subjects

P Doevendans

Publications and source records attributed to P Doevendans.

10 recordsLinked to original sources

PubMed2003

Stem cell-derived angiogenic/vasculogenic cells: possible therapies for tissue repair and tissue engineering.

1. The recent ability to isolate stem cells and study their specific capacity of self-renewal with the formation of different cell types has opened up exciting vistas to help the repair of damaged tissue and even the formation of new tissue. In the present review, we deal with the characteristics and sources that stem cells can be derived and cultured from. 2. We focus on the role that stem cell-derived vascular cells or endothelial progenitor cells (EPC) may play in (re)vascularization of ischaemic and engineered tissues. This so-called vasculogenesis resembles the embryological process in which 'haemangioblasts' differentiate in blood cells, as well as in primitive vessels. Although also derived from the blood-forming bone marrow, in adult life vasculogenic stem cells contribute only little to the regular vascular repair mechanisms: namely (i) angiogenesis (outgrowth of vessels from existing vessels); and (ii) arteriogenesis (monocyte-aided increase in the calibre of existing arteriolar collaterals). 3. Most attempts to increase vascular repair by stem cells involve the use of growth factors, which mobilize stem cells from bone marrow into the blood, sometimes combined with isolation and reinfusion of these cells after ex vivo expansion and differentiation into EPC. 4. Clear improved perfusion of ischaemic sites and new vasculature has been observed in vivo mostly in animal models. Specific homing or administration of these cells and regulated and quantitative expansion and (final) differentiation at these vascular (repair) sites are less studied, but are paramount for efficacy and safety. 5. In conclusion, the use of embryonic stem cells will still encounter ethical objections. Moreover, special attention and measures are needed to cope with the allogeneic barriers that these cells usually encounter. In general, the long and complicated ex vivo cultures to obtain sufficient offspring from the very small numbers of stem cells that can be obtained as starting material will be costly and cumbersome. Both basic research on conceptual matters and cost-effective development of the product itself will have to go a long way before the clinical use of some volume can be expected.

Animals↗

PubMed2000

Structure and chromosome location of Smtn, the mouse smoothelin gene.

Smoothelins are cytoskeleton-associated proteins that are found in contractile smooth muscle. Two isoforms have been identified: smoothelin-A, expressed in visceral tissues and smoothelin-B, found in vascular tissues. The mouse smoothelin gene (Smtn) was isolated and characterized. It was assigned to chromosome 11 band A2-A3 by fluorescence in situ hybridization. The gene consists of 20 exons and spans 23 kb. Its structure is conserved between mouse and human. The proximal promoter of both smoothelin-A and smoothelin-B contains several transcription factor-binding sites but lacks a consensus TATA box.

Animals↗

PubMed1999

Atherosclerosis in APOE*3-Leiden transgenic mice: from proliferative to atheromatous stage.

BACKGROUND: This study documents (1) the progression of atherosclerosis along the entire arterial tree in APOE*3-Leiden mice after 1, 4, 6, 9, and 12 months of a high-fat/high-cholesterol (HFC) diet and (2) the amount and phenotype of DNA-synthesizing and apoptotic cells in different lesion types after 6 months of HFC diet. METHODS AND RESULTS: Diet duration was correlated with a craniocaudal progression of lesion development and with an increase in severity of the lesion. Typically, the lesions contained smooth muscle cells, macrophages, and T lymphocytes and were covered by an intact endothelium. Whereas DNA synthesis (BrdU uptake) was usually elevated in type II lesions (8.6+/-0.8% versus 1.0+/-0.2% in the nondiseased arterial wall; P<0.05), apoptosis was found primarily in advanced lesions (type IV, 1.3+/-0.1% and type V, 1.2+/-0.2% versus 0.04+/-0.04% in the nondiseased arterial wall [P<0.05]). Cell phenotyping revealed that the majority of DNA synthesis and apoptosis was confined to the macrophage-derived foam cell (68.6+/-3. 0% and 82.2+/-4.6%, respectively). CONCLUSIONS: This study shows that in APOE*3-Leiden mice, duration of an HFC diet is associated with (1) a craniocaudal progression of lesion development and (2) an increased complexity of atherosclerotic lesions. Furthermore, DNA synthesis is predominant in early lesions, whereas apoptosis is present mainly in more advanced lesions. Both parameters of cell turnover are confined primarily to the macrophage-derived foam cell.

Animals↗

PubMed1999

Novel KCNQ1 and HERG missense mutations in Dutch long-QT families.

Congenital long QT syndrome (cLQTS) is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncopes, seizure, or sudden death. LQTS can occur either as an autosomal dominant (Romano Ward) or as an autosomal recessive disorder (Jervell and Lange-Nielsen syndrome). Mutations in at least five genes have been associated with the LQTS. Four genes, encoding cardiac ion channels, have been identified. The most common forms of LQTS are due to mutations in the potassium-channel genes KCNQ1 and HERG. We have screened 24 Dutch LQTS families for mutations in KCNQ1 and HERG. Fourteen missense mutations were identified. Eight of these missense mutations were novel: three in KCNQ1 and five in HERG. Novel missense mutations in KCNQ1 were Y184S, S373P, and W392R and novel missense mutations in HERG were A558P, R582C, G604S, T613M, and F640L. The KCNQ1 mutation G189R and the HERG mutation R582C were detected in two families. The pathogenicity of the mutations was based on segregation in families, absence in control individuals, the nature of the amino acid substitution, and localization in the protein. Genotype-phenotype studies indicated that auditory stimuli as trigger of cardiac events differentiate LQTS2 and LQTS1. In LQTS1, exercise was the predominant trigger. In addition, a number of asymptomatic gene defect carriers were identified. Asymptomatic carriers are still at risk of the development of life-threatening arrhythmias, underlining the importance of DNA analyses for unequivocal diagnosis of patients with LQTS.

Cation Transport Proteins↗

PubMed1997

Developmental expression of the murine spliceosome-associated protein mSAP49.

We have isolated the mouse homologue of human spliceosome-associated protein SAP49, mSAP49. mSAP49 contains two RNA recognition motifs (RRM) in the N terminus of the predicted amino acid sequence, and a highly basic C terminus rich in glycine/proline. mSAP49 displayed a plastic of expression in cardiac development. In the adult mouse, mSAP49 is widely distributed, although it was found at relatively lower levels in the heart. In situ hybridization analysis of mSAP49 mRNA distribution in staged mouse embryos showed that mSAP49 onset occurs later in the heart than in other embryonic tissues. While mSAP49 expression was found at day 10.0 postconception (pc) in the optic eminence, optic vesicle, hindbrain, and somites, it was not in cardiac structures. mSAP49 was detected in the ventricles at day 11.5, and at day 13.5 it was also detected in the atria. Northern analysis showed that mSAP49 mRNA displayed a peak of expression in the heart at days 14.0-15.0 pc, and its abundance decayed in the adult. This dynamic pattern of cardiac expression suggests that mSAP49 may be contributing to a change in the ratio of spliceosome components during cardiac growth and development, which may have consequences for tissue-specific splicing, RNA stabilization, or translation.

Amino Acid Sequence↗

PubMed1997

Arrhythmia risk: electrophysiological studies and monophasic action potentials.

Shortly after in the introduction of programmed electrical stimulation (PES) of the heart to study and localize cardiac arrhythmias in the intact human heart, the technique was used for risk stratification of the arrhythmia patient. Two decades later we have to conclude that especially in ventricular arrhythmias the technique of PES did not live up to our expectations and the left ventricular function is a better long-term predictor than the induction of ventricular arrhythmias or the ability to find an antiarrhythmic drug able to prevent the initiation of the classically documented ventricular arrhythmia. Another sobering finding came from the analysis of the characteristics of the patient dying suddenly out-of-hospital, which showed that most of those patients could not be classified before the event as being at high risk using noninvasive or invasive testing, not even in those with a previous cardiac history. Monomorphic action potential (MAP) recordings have been of importance in our understanding of torsade de pointe arrhythmias in congenital and acquired QT prolongation. A major problem in case of a less generalized electrophysiological abnormality is the identification of the appropriate place where to put the MAP-electrode.

Action Potentials↗

PubMed1996

Developmental changes in ionic channel activity in the embryonic murine heart.

We have isolated murine embryonic atrial and ventricular cells derived from timed-pregnant females at different periods and used patch-clamp procedures to investigate age- and chamber-specific expression of ionic channels in the developing fetal mouse. Our data indicate that L-type Ca2+ channels play a dominant role in excitation during early murine cardiac embryogenesis and that Na+ channel expression increases dramatically just before birth. K+ channel expression is particularly sensitive to changes during development. Neither atrial nor ventricular cells express a slowly activating component of delayed rectification (IKs) until just before birth, and inwardly rectifying channel activity, associated with determination of cellular resting potential, is not markedly apparent until late stages of embryogenesis. Instead, we find robust expression of the ATP-regulated K+ channel at early and late states of embryonic development, which may indicate a novel functional role for this channel during morphogenesis of the heart. These results have important implications for the physiology and development of the murine cardiac conduction system and will also serve as a baseline for future studies designed to investigate developmental changes of ion channel expression in the myocardium of both wild-type and genetically modified mice.

Adenosine Triphosphate↗

PubMed1994

Factors influencing changes in the signal-averaged electrocardiogram within the first year after a first myocardial infarction.

One hundred twenty-nine patients were prospectively studied after a first myocardial infarction. A first signal-averaged electrocardiogram (SAECG-1) was performed in the acute phase (within 48 hours after onset of symptoms) and a second one (SAECG-2) in the late phase (6 to 18 months after hospital discharge). We studied the influence of nine parameters on the evolution of the signal-averaged electrocardiogram: age, gender, myocardial infarction location, number of diseased coronary vessels, infarct-related coronary artery patency, use of thrombolytic therapy or percutaneous transluminal coronary angioplasty in the acute phase, left ventricular ejection fraction, and recurrence of ischemic events. No follow-up data were available in 15 patients. Of the remaining 114 patients, an ischemic event occurred in 25 (22%). The signal-averaged electrocardiogram remained unchanged in 97 (85%) (remaining normal in 78 and abnormal in 19). It became abnormal in 13 (11.5%) and became normal in 4 (3.5%). In patients with a normal SAECG-1, two factors were associated with the change to an abnormal SAECG-2: (1) an ischemic event occurred in 11 (85%) of 13 patients whose SAECG-2 was abnormal compared with only 13 (17%) of 78 patients whose SAECG-2 remained normal (p < 0.0001), and (2) 100% of patients with an abnormal SAECG-2 had an inferior myocardial infarction compared with 54% of patients with a normal SAECG-2 (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

Effects on the signal-averaged electrocardiogram of opening the coronary artery by thrombolytic therapy or percutaneous transluminal coronary angioplasty during acute myocardial infarction.

One hundred twenty-nine patients were retrospectively analyzed and divided into 3 groups according to (1) the presence of a patent artery obtained either spontaneously or after thrombolytic therapy but without percutaneous transluminal coronary angioplasty (PTCA) (group I, n = 83), (2) the presence of a patent artery after opening by PTCA (group II, n = 29), or (3) absence of reperfusion despite thrombolytic therapy or PTCA (group III, n = 17). Thrombolytic therapy was given within 4 hours after onset of symptoms (mean 2.5 +/- 1.0 hours) and PTCA was performed within 24 hours after the onset of symptoms (mean 6 +/- 6 hours). Signal averaging was performed within 24 hours after cardiac catheterization. An abnormal signal-averaged electrocardiogram was present in 10 of 83 (12%) group I, 9 of 29 (31%) group II and 7 of 17 (41%) group III patients (p < 0.05 group I vs II, p < 0.01 group I vs III, no statistical difference group II vs III). Therefore, in contrast to reperfusion by thrombolytic therapy the incidence of abnormalities on the signal-averaged electrocardiogram early after myocardial infarction is not reduced by an early opening of the culprit vessel by PTCA.

Angioplasty, Balloon, Coronary↗

PubMed1993

Echocardiographic wall motion abnormalities and the signal averaged electrocardiogram in the acute phase of a first myocardial infarction.

We studied the relationship between wall motion abnormalities determined by echocardiography and the signal-averaged electrocardiogram in 82 consecutive patients during the acute phase of a first myocardial infarction. An abnormal signal-averaged electrocardiogram was defined as the presence of two of the following criteria: a QRS duration > or = 114 ms, a root mean square voltage (RMS) of the last 40 ms < or = 25 microV and an amplitude signal lower than 40 microV lasting > or = 39 ms. The left ventricle was divided into 13 segments and the contraction pattern divided into akinesia alone (including dyskinesia) (group A), hypokinesia alone (group B) and both hypokinesia and akinesia (group C). An abnormal signal-averaged electrocardiogram was found in 14/82 patients (17%) and was correlated with the persistence of occlusion of the infarct-related vessel (32% vs 9%, P < 0.02). In patients with a patent vessel, the incidence of an abnormal signal-averaged electrocardiogram was 14% in group A, 9% in group B and 0% in group C (NS). In patients with an occluded vessel an abnormal signal-averaged electrocardiogram was found in 10% of group A patients, in 36% in group B patients and in 75% of group C patients (P = 0.05). Our study suggests that the presence of hypokinetic areas during the acute phase of a first myocardial infarction and an abnormal signal-averaged electrocardiogram indicate an occluded infarct-related vessel.

Aged↗