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Biomedical subjects

Giulio Pompilio

Publications and source records attributed to Giulio Pompilio.

16 recordsLinked to original sources

Left common carotid artery as inflow site in coronary artery bypass grafting.

Porcelain aorta is associated to significantly increased risk of atheromatous embolization in patients who undergo cardiac surgery. We described three cases in which coronary artery bypass grafting was performed off-pump and the saphenous vein graft was anastomosed proximally to the left common carotid artery. This technique permitted avoidance of ascending aortic manipulation and reduce the risk of atheromatous embolization.

Aged↗

Exogenous high-mobility group box 1 protein induces myocardial regeneration after infarction via enhanced cardiac C-kit+ cell proliferation and differentiation.

High-mobility group box 1 protein (HMGB1) is a chromatin protein that is released by inflammatory and necrotic cells. Extracellular HMGB1 signals tissue damage, stimulates the secretion of proinflammatory cytokines and chemokines, and modulates stem cell function. The present study examined exogenous HMGB1 effect on mouse left-ventricular function and myocyte regeneration after infarction. Myocardial infarction was induced in C57BL/6 mice by permanent coronary artery ligation. After 4 hours animals were reoperated and 200 ng of purified HMGB1 was administered in the peri-infarcted left ventricle. This intervention resulted in the formation of new myocytes within the infarcted portion of the wall. The regenerative process involved the proliferation and differentiation of endogenous cardiac c-kit+ progenitor cells. Circulating c-kit+ cells did not significantly contribute to HMGB1-mediated cardiac regeneration. Echocardiographic and hemodynamic parameters at 1, 2, and 4 weeks demonstrated a significant recovery of cardiac performance in HMGB1-treated mice. These effects were not observed in infarcted hearts treated either with the unrelated protein glutathione S-transferase or a truncated form of HMGB1. Thus, HMGB1 appears to be a potent inducer of myocardial regeneration following myocardial infarction.

Animals↗

Electrophysiological properties of mouse bone marrow c-kit+ cells co-cultured onto neonatal cardiac myocytes.

OBJECTIVE: Controversy about hematopoietic stem cells reprogramming into cardiac myocytes is currently supported by positive and negative findings. In fact, some reports have shown the ability of stem cells from the bone marrow (BM) to differentiate into cardiac myocytes and to contribute to myocardium repair, while others have reported the opposite. METHODS: C-kit(+) cells from mouse bone marrow were co-cultured onto neonatal cardiac myocytes. Hematopoietic stem cell-derived cells were analyzed by investigating the expression of cardiac markers and ion channels and by single-cell electrophysiological recordings. RESULTS: Groups of undifferentiated c-kit(+) cells displayed only outward currents. Co-cultured c-kit(+) stem cells on neonatal cardiac myocytes expressed cardiac markers and Na(+) and Ca(2+) voltage-gated ion channels. However, Na(+) and Ca(2+) currents were not detected by electrophysiological patch-clamp recordings even if caffeine and cyclopiazonic acid treatment showed the presence of intracellular calcium stores. This suggests that these channels, although expressed, were not functional and thus do not allow the coupling between excitation and contraction that is typical of cardiac myocytes. Nevertheless, co-cultured cells had a more hyperpolarized resting membrane potential and, at least in a subset of cells, displayed voltage-gated inward rectifier currents and outward currents. Co-cultured c-kit(+)-derived cells were not connected to surrounding cardiac myocytes through gap junctions. To induce a more pronounced differentiation, co-cultured cells were treated with BMP-4 and TGF-beta, two factors that were shown to trigger a cardiac myocyte differentiation pathway in embryonic stem (ES) cells. Even under these conditions, c-kit(+) cells did not differentiate into functionally active cardiac myocytes. However, TGF-beta/BMP-4-treated cells were hyperpolarized and showed and increased inward rectifier current density. CONCLUSIONS: Our study shows that mouse BM hematopoietic stem cells exhibit a limited plasticity to transdifferentiate into cardiac myocytes in culture.

Animals↗

Invited commentary.

Explore the source record for details and available documents.

Coronary Artery Bypass↗

Hypoxia inhibits myogenic differentiation through accelerated MyoD degradation.

Cells undergo a variety of biological responses when placed in hypoxic conditions, including alterations in metabolic state and growth rate. Here we investigated the effect of hypoxia on the ability of myogenic cells to differentiate in culture. Exposure of myoblasts to hypoxia strongly inhibited multinucleated myotube formation and the expression of differentiation markers. We showed that hypoxia reversibly inhibited MyoD, Myf5, and myogenin expression. One key step in skeletal muscle differentiation involves the up-regulation of the cell cycle-dependent kinase inhibitors p21 and p27 as well as the product of the retinoblastoma gene (pRb). Myoblasts cultured under hypoxic conditions in differentiation medium failed to up-regulate both p21 and pRb despite the G1 cell cycle arrest, as evidenced by p27 accumulation and pRb hypophosphorylation. Hypoxia-dependent inhibition of differentiation was associated with MyoD degradation by the ubiquitin-proteasome pathway. MyoD overexpression in C2C12 myoblasts overrode the differentiation block imposed by hypoxic conditions. Thus, hypoxia by inducing MyoD degradation blocked accumulation of early myogenic differentiation markers such as myogenin and p21 and pRb, preventing both permanent cell cycle withdraw and terminal differentiation. Our study revealed a novel anti-differentiation effect exerted by hypoxia in myogenic cells and identified MyoD degradation as a relevant target of hypoxia.

Animals↗

Autologous peripheral blood stem cell transplantation for myocardial regeneration: a novel strategy for cell collection and surgical injection.

PURPOSE: Bone-marrow and peripheral blood-derived stem cells can be used as stimulators of myogenesis and angiogenesis. We describe an original technique for collection and surgical intramyocardial injection of peripheral blood-derived stem cells. DESCRIPTION: Stem cells are mobilized from the bone marrow by means of subcutaneous administration of Lenogastrim (Granocyte 34 [Aventis Pharma, Milan, Italy]) for 4 days. Then the day before the operation the peripheral blood-derived stem cells are collected by means of apheresis and processed in order to obtain the CD 133+ cells. Cells are injected into the myocardium in a beating heart in order to induce angiogenesis locally or myogenesis, or both. When necessary, off-pump coronary artery bypass grafting is previously accomplished. EVALUATION: Thus far we have investigated 4 patients (3 patients who have received off-pump peripheral blood stem cell injection and coronary bypass grafting through median sternotomies, and 1 patient who underwent cell transplant alone through a minimally-invasive transdiaphragmatic approach). No complications were noted at a mean of 4 months after surgery. CONCLUSIONS: This novel method of peripheral bone marrow stem cell collection and intramyocardial injection seems to be safe, feasible, and reproducible. However, there is need of further evidence to definitely assess safety issues and clinical results.

AC133 Antigen↗

Six-year monitoring of the donor-specific immune response to cryopreserved aortic allograft valves: implications with valve dysfunction.

BACKGROUND: The immune rejection has been anticipated as one of the major causes of allograft aortic valve (AAV) degeneration. The purpose of this study was to prospectively serially measure the magnitude and evolution of the recipient anti-HLA class I antibody response up to 6 years from AAV implant and to correlate serologic data with valve performance by means of a concurrent echocardiographic survey. METHODS: Cryopreserved AAVs were obtained from multiorgan HLA-typed donors. Nineteen patients younger than 50 years (mean age, 43.3 +/- 8 years) were prospectively studied. After successful surgery, all AAV recipient underwent at 3 and 6 months and each year postoperatively (mean follow-up, 71.9 months) concomitant serum sample collection and two-dimensional transthoracic echocardiography. The presence of anti-HLA antibodies was tested against a panel of lymphocytes obtained from 30 blood donors. RESULTS: Progressive structural valve deterioration was seen in 6 patients (31.5%) of whom 4 (21%) were reoperated. All pretransplant recipients sera were panel-reactive antibody negative. Seventeen patients (89.4%) demonstrated significant panel-reactive antibody levels, which peaked at 6 months postoperatively, declined from 6 to 24 months, and slowly decreased afterward. In 14 of 19 cases (73.6%) donor-specific HLA antibodies were identified. A strong immunization (6-year persistence of panel-reactive antibody > 70% and peak panel-reactive antibody > 80%) was detected in 31.5% and 36.8% of recipients, respectively. Strong immunization was found to be significantly associated with progressive structural deterioration. CONCLUSIONS: The immune reaction after cryopreserved AAV implantation is a peculiar long-lasting response occurring in the majority of recipients younger than 50 years of age. An association between a sustained and pronounced immunization and an aggressive AAV degeneration was observed.

Adolescent↗

Current perceptions of cardiovascular gene therapy.

Due to differences in their knowledge base, scientists, health care professionals, and the general public have varying perceptions of the expectations and risks of using gene therapy for the treatment of cardiovascular disease. Gene therapists are aware of the importance of selecting the right vector, the right gene, and the right administration procedure for a specific application and for characterization of the heterogeneity of the physiologic response to gene expression. They also recognize the need for large-scale clinical trials to demonstrate short- and long-term safety, in addition to efficacy, for widespread acceptance. Interventional cardiologists are more likely to judge a therapy primarily on its ability to improve cardiovascular pathophysiology and function, although they too will demand safety data. Once convinced of the benefits of a gene therapy, interventional cardiologists will rely on regulatory and reimbursement authorities to approve the procedure. Attitudes of less-specialized physicians toward gene therapy and, specifically, therapeutic angiogenesis will be influenced by the level of clinical trial activity in their country and opinions expressed in the media. However, all will want safety and efficacy data as well as clear guidance on the type of patients who should be referred for treatment. Nurses' roles are set to expand with the introduction of gene-based therapies; most will need further genetics education to rise to these challenges with confidence. The success of a gene therapy will also rely on patients' perceptions and their willingness to receive the treatment. Any misconceptions based on unreliable information sources need to be addressed.

Attitude↗

Myoendothelial differentiation of human umbilical cord blood-derived stem cells in ischemic limb tissues.

Human umbilical cord blood (UCB) contains high numbers of endothelial progenitors cells (EPCs) characterized by coexpression of CD34 and CD133 markers. Prior studies have shown that CD34+/CD133+ EPCs from the cord or peripheral blood (PB) can give rise to endothelial cells and induce angiogenesis in ischemic tissues. In the present study, it is shown that freshly isolated human cord blood CD34+ cells injected into ischemic adductor muscles gave rise to endothelial and, unexpectedly, to skeletal muscle cells in mice. In fact, the treated limbs exhibited enhanced arteriole length density and regenerating muscle fiber density. Under similar experimental conditions, CD34- cells did not enhance the formation of new arterioles and regenerating muscle fibers. In nonischemic limbs CD34+ cells increased arteriole length density but did not promote formation of new muscle fibers. Endothelial and myogenic differentiation ability was maintained in CD34+ cells after ex vivo expansion. Myogenic conversion of human cord blood CD34+ cells was also observed in vitro by coculture onto mouse myoblasts. These results show that human cord blood CD34+ cells differentiate into endothelial and skeletal muscle cells, thus providing an indication of human EPCs plasticity. The full text of this article is available online at http://www.circresaha.org.

Animals↗

Lack of association between serum immunoreactivity and Chlamydia pneumoniae detection in the human aortic wall.

BACKGROUND: Only a few studies have focused the attention on the relation between elevated anti-Chlamydia pneumoniae (CP) antibodies and the detection of CP in the arterial wall. The aim of our study is thus to investigate the relationship between immune response to CP and detection of CP in the aortic walls of patients with abdominal aortic aneurysm. METHODS AND RESULTS: A specimen of aortic wall was obtained from 102 consecutive patients who underwent abdominal aneurysm repair. The possible presence of CP was studied by polymerase chain reaction and confirmed by nonradioactive DNA hybridization. Antibody response to CP was studied (IgG, IgA titers). We found 33 patients (32.4%) with CP DNA+. No correlation between CP DNA detection and antibody titers was found (IgG P=0.52, IgA P=0.66). High correlation between IgG and IgA titer was observed (P<0.01). Endovascular presence of CP and antibody titers was not related to the age of the patient. CONCLUSIONS: CP antibody titers are not associated with the presence of CP in the aortic wall of patients with abdominal aortic aneurysm.

Antibodies, Bacterial↗

Different effects of high and low shear stress on platelet-derived growth factor isoform release by endothelial cells: consequences for smooth muscle cell migration.

In the present study, we analyzed the effect of conditioned media (CM) from bovine aortic endothelial cells exposed to laminar shear stress (SS) of 5 dyne/cm2 (SS5) or 15 dyne/cm2 (SS15) for 16 hours on smooth muscle cell (SMC) migration. In response to CM from bovine aortic endothelial cells exposed to SS5 (CMSS5) and SS15 (CMSS15), migration was 45 +/- 5.5 and 30 +/- 1.5 cells per field, respectively (P<0.05). Similar results were obtained with SS of 2 versus 20 dyne/cm2 and also when SS of 5 and 15 dyne/cm2 lasted 24 hours. Platelet-derived growth factor (PDGF)-AA levels in CMSS5 and CMSS15 were 9 +/- 7 and 18 +/- 5 ng/10(6) cells for 16 hours, respectively (P<0.05); PDGF-BB levels in CMSS5 and CMSS15 were 38 +/- 10 and 53 +/- 10 ng/10(6) cells for 16 hours, respectively (P<0.05). PDGF receptor alpha (PDGFRalpha) and PDGF receptor beta (PDGFRbeta) in SMCs were phosphorylated by CMSS15>CMSS5. In response to CMSS15, a neutralizing antibody against PDGF-AA enhanced SMC migration to a level comparable to that of CMSS5; in contrast, antibodies against PDGF-BB abolished SMC migration. Transfection of SMCs with a dominant-negative PDGFRalpha or PDGFRbeta increased or inhibited, respectively, SMC migration in response to CMSS15. Overexpression of wild-type PDGFRalpha inhibited SMC migration in response to CMSS5, CMSS15, or recombinant PDGF-BB (P<0.001). These results suggest that the ability of high SS to inhibit arterial wall thickening in vivo may be related to enhanced activation of PDGFRalpha in SMCs by PDGF isoforms secreted by the endothelium.

Animals↗

Acute effects of 17beta-estradiol on left internal mammary graft after coronary artery bypass grafting.

BACKGROUND: Vasospasm of arterial conduits used for coronary surgical procedures is an important cause of postoperative graft failure. Mounting experimental evidence suggests that estrogen reverses acetylcholine-induced vasospasm of the coronary arteries in animals and humans. Estrogen also affects endothelium-derived constrictor factors. We therefore investigated the in vivo vasomotor responses to transdermal 17beta-estradiol of the left internal mammary artery (LIMA) grafted on the anterior descending coronary artery. METHODS: We studied 20 women, mean age of 62 +/- 7.2 years (range, 48 to 73 years), who had undergone cardiopulmonary bypass for coronary artery bypass grafting. They received transdermal 17beta-estradiol on the fifth day after operation. The diameter, cross-sectional area, and blood flow of the LIMA graft were measured by transthoracic color Doppler echography before (basal values) and after the transdermal administration of 50 microg of 17beta-estradiol (control). RESULTS: LIMA graft vasodilation after the administration of 17beta-estradiol was observed. A significant increase in diameter (2.06 +/- 0.4 mm versus 2.37 +/- 0.28 mm; p = 0.035) and cross-sectional area (3.45 +/- 1. 2 mm2 versus 4.24 +/- 1 mm2; p = 0.039) was registered. The LIMA graft mean flow increased by 49% (44.76 +/- 27.19 mL/min versus 56.62 +/- 27.69 mL/min), but this increase was not statistically significant (p = 0.06). CONCLUSIONS: The acute postoperative transdermal administration of 17beta-estradiol induced a significant increase of LIMA graft diameter and cross-sectional area in postmenopausal women who underwent coronary artery bypass grafting. The LIMA graft vasodilation was also associated with an improvement in LIMA blood flow.

Administration, Cutaneous↗

[Autologous cellular cardiomyoplasty in humans: can we hit the mark?].

Myocardial cell therapy is a new promising therapeutic option for patients with heart failure. In this paper, we review the main experimental evidences and the first clinical researches in this field. Moreover, a comment on the theoretical and practical aspects for a pilot clinical use and a glance to the future are also provided.

Cell Transplantation↗