http://hdl.handle.net/10993/95 Search this channel search https://orbilu.uni.lu/simple-search http://hdl.handle.net/10993/42780 Title: A Pathway to Keep All Lifelong Learners Up to Date: The ERS Continuing Professional Development Programme <br/> <br/>Author, co-author: Farr, Amy; Aliberti, Stefano; Loukides, Stelios; Massard, Gilbert; Primhak, Robert; Rohde, Gernot G U; Tabin, Nathalie; Pannetier, Carine; Stolz, Daiana Tue, 10 Mar 2020 12:15:19 GMT http://hdl.handle.net/10993/42553 Title: The microbiome of the human lower airways: a next generation sequencing perspective <br/> <br/>Author, co-author: Aho, Velma; Pereira, P. A. B.; Haahtela, T.; Pawankar, R.; Auvinen, P.; Koskinen, K. Tue, 18 Feb 2020 14:28:40 GMT http://hdl.handle.net/10993/33055 Title: A physician who has crossed many frontiers and has changed direction a number of times  <br/> <br/>Author, co-author: Ozkan, Judith; Neyses, Ludwig Fri, 17 Nov 2017 04:30:03 GMT http://hdl.handle.net/10993/31992 Title: Selective inhibition of plasma membrane calcium ATPase 4 improves angiogenesis and vascular reperfusion <br/> <br/>Author, co-author: Kurusamy, Sathishkumar; López-Maderuelo, Dolores; Little, Robert; Cadagan, David; Savage, Aaron M.; Ihugba, Jude C.; Baggott, Rhiannon R.; Rowther, Farjana B.; Martínez-Martínez, Sara; Gómez-del Arco, Pablo; Murcott, Clare; Wang, Weiguang; Nistal, J. Francisco; Oceandy, Delvac; Neyses, Ludwig; Wilkinson, Robert N.; Cartwright, Elizabeth J.; Redondo, Juan Miguel; Armesilla, Angel Luis <br/> <br/>Abstract: AIMS: Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of ischaemic tissues in patients. Failure to restore efficient VEGF activity in the ischaemic organ remains a major problem in current pro-angiogenic therapeutic approaches. Plasma membrane calcium ATPase 4 (PMCA4) negatively regulates VEGF-activated angiogenesis via inhibition of the calcineurin/NFAT signalling pathway. PMCA4 activity is inhibited by the small molecule aurintricarboxylic acid (ATA). We hypothesize that inhibition of PMCA4 with ATA might enhance VEGF-induced angiogenesis. METHODS AND RESULTS: We show that inhibition of PMCA4 with ATA in endothelial cells triggers a marked increase in VEGF-activated calcineurin/NFAT signalling that translates into a strong increase in endothelial cell motility and blood vessel formation. ATA enhances VEGF-induced calcineurin signalling by disrupting the interaction between PMCA4 and calcineurin at the endothelial-cell membrane. ATA concentrations at the nanomolar range, that efficiently inhibit PMCA4, had no deleterious effect on endothelial-cell viability or zebrafish embryonic development. However, high ATA concentrations at the micromolar level impaired endothelial cell viability and tubular morphogenesis, and were associated with toxicity in zebrafish embryos. In mice undergoing experimentally-induced hindlimb ischaemia, ATA treatment significantly increased the reperfusion of post-ischaemic limbs. CONCLUSIONS: Our study provides evidence for the therapeutic potential of targeting PMCA4 to improve VEGF-based pro-angiogenic interventions. This goal will require the development of refined, highly selective versions of ATA, or the identification of novel PMCA4 inhibitors. Tue, 29 Aug 2017 11:05:07 GMT http://hdl.handle.net/10993/29627 Title: Effect of renal artery revascularization upon cardiac structure and function in atherosclerotic renal artery stenosis: cardiac magnetic resonance sub-study of the ASTRAL trial. <br/> <br/>Author, co-author: Ritchie, James; Green, Darren; Chrysochou, Tina; Hegarty, Janet; Handley, Kelly; Ives, Natalie; Wheatley, Keith; Houston, Graeme; Wright, Julian; Neyses, Ludwig; Chalmers, Nicholas; Mark, Patrick; Patel, Rajan; Moss, Jon; Roditi, Giles; Eadington, David; Lukaschuk, Elena; Cleland, John; Kalra, Philip A. <br/> <br/>Abstract: BACKGROUND: Cardiac abnormalities are frequent in patients with atherosclerotic renovascular disease (ARVD). The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial studied the effect of percutaneous renal revascularization combined with medical therapy compared with medical therapy alone in 806 patients with ARVD. METHODS: This was a pre-specified sub-study of ASTRAL (clinical trials registration, current controlled trials number: ISRCTN59586944), designed to consider the effect of percutaneous renal artery angioplasty and stenting on change in cardiac structure and function, measured using cardiac magnetic resonance (CMR) imaging. Fifty-one patients were recruited from six selected ASTRAL centres. Forty-four completed the study (medical therapy n = 21; revascularization n = 23). Full analysis of CMR was possible in 40 patients (18 medical therapy and 22 revascularization). CMR measurements of left and right ventricular end systolic (LV and RVESV) and diastolic volume (LV and RVEDV), ejection fraction (LVEF) and mass (LVM) were made shortly after recruitment and before revascularization in the interventional group, and again after 12 months. Reporting was performed by CMR analysts blinded to randomization arm. RESULTS: Groups were well matched for mean age (70 versus 72 years), blood pressure (148/71 versus 143/74 mmHg), degree of renal artery stenosis (75 versus 75%) and comorbid conditions. In both randomized groups, improvements in cardiac structural parameters were seen at 12 months, but there were no significant differences between treatment groups. Median left ventricular changes between baseline and 12 months (medical versus revascularization) were LVEDV -1.9 versus -5.8 mL, P = 0.4; LVESV -2.1 versus 0.3 mL, P = 0.7; LVM -5.4 versus -6.3 g, P = 0.8; and LVEF -1.5 versus -0.8%, P = 0.7. Multivariate regression also found that randomized treatment assignment was not associated with degree of change in any of the CMR measurements. CONCLUSIONS: In this sub-study of the ASTRAL trial, renal revascularization did not offer additional benefit to cardiac structure or function in unselected patients with ARVD. <br/> <br/>Commentary: (c) The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. Mon, 06 Feb 2017 14:19:47 GMT http://hdl.handle.net/10993/29205 Title: Polonium 210: is it possible to decrease the risk for smokers? <br/> <br/>Author, co-author: Zaga, Vicenzo; Lygidakis, Charilaos Thu, 29 Dec 2016 12:40:25 GMT http://hdl.handle.net/10993/28429 Title: The German Centre for Cardiovascular Research. <br/> <br/>Author, co-author: Prendergast, Bernard; Coope, Leslie T.; Crijns, Harry; Falkenstein, Elisabeth; Folsch, Ulrich; Halvorsen, Sigrun; Janssens, Stefan; Jokinen, Eero; Kroemer, Heyo K.; Lucke, Anne; Murer, Heini; Nagel, Eike; Neyses, Ludwig; Perk, Joep; Probst-Hensch, Nicole; Rietschel, Ernst Th; Rutten, Hartmut; Steingen, Caroline; Tedgui, Alain; van Gilst, Wiek; Eschenhagen, Thomas; Kristensen, Steen Dalby Tue, 20 Sep 2016 13:31:03 GMT http://hdl.handle.net/10993/27836 Title: Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomized controlled trials <br/> <br/>Author, co-author: Neyses, Ludwig; Mamas, MA Mon, 04 Jul 2016 12:10:07 GMT http://hdl.handle.net/10993/27835 Title: Cardiac metabolism; from bench to bedside: Diabetic cardiomyopathy, a disease of cardiac metabolism? <br/> <br/>Author, co-author: Neyses, Ludwig <br/> <br/>Abstract: The study of diabetic cardiomyopathy is an area of significant interest given the strong association between diabetes and the risk of heart failure. Many unanswered questions remain regarding the clinical definition and pathogenesis of this metabolic cardiomyopathy. This article reviews the current understanding of diabetic cardiomyopathy with a particular emphasis on the unresolved issues that have limited translation of scientific discovery to patient bedside. <br/> <br/>Commentary: Copyright (c) 2012 Elsevier Inc. All rights reserved. Mon, 04 Jul 2016 12:09:39 GMT http://hdl.handle.net/10993/27834 Title: Use of the Sideguard (Cappella) stent in bifurcation lesions: a real-world experience. <br/> <br/>Author, co-author: Mamas, Mamas A.; Farooq, Vasim; Latib, Azeem; Sastry, Sanjay; D'Souza, Savio; Williams, Paul; Wiper, Andrew; Neyses, Ludwig; El-Omar, Magdi; Fraser, Doug G.; Fath-Ordoubadi, Farzin <br/> <br/>Abstract: AIMS: The Sideguard(R) stent (Cappella Medical Devices Ltd, Galway, Ireland), is a novel nitinol self-expanding dedicated bifurcation stent that flares proximally at the ostium of the side branch (SB) into a trumpet shape thereby achieving full ostial coverage. The aim of this study is to report the utility and limitations of this stent in patients undergoing treatment to bifurcation coronary lesions in a real-world setting. METHODS AND RESULTS: We prospectively identified 20 successive patients admitted over a 6-month period in whom there was significant SB disease and who were suitable for a bifurcation procedure. The Sideguard(R) stent was successfully used in all 20 cases including several that would have been technically difficult using conventional bifurcation techniques. We highlight use of this system using five illustrative cases that illustrate its utility and limitations in the treatment of bifurcation lesions. CONCLUSIONS: The Sideguard(R) stent can be used to treat complex bifurcation lesions in a straight forward manner and is not subject to the limitations associated with conventional bifurcation PCI techniques including jailing of the SB ostium and inability to fully cover/scaffold the ostium of the SB. Mon, 04 Jul 2016 12:09:26 GMT http://hdl.handle.net/10993/27833 Title: Activation of sphingosine-1-phosphate signalling as a potential underlying mechanism of the pleiotropic effects of statin therapy. <br/> <br/>Author, co-author: Egom, Emmanuel E.; Rose, Robert A.; Neyses, Ludwig; Soran, Handrean; Cleland, John G. F.; Mamas, Mamas A. <br/> <br/>Abstract: The mechanisms by which statins are beneficial are incompletely understood. While the lowering of low-density lipoprotein concentration is associated with regression of atherosclerosis, the observed benefit of statin therapy begins within months after its initiation, making regression an unlikely cause. Although LDL-C lowering is the main mechanism by which statin therapy reduces cardiovascular events, evidence suggests that at least some of the beneficial actions of statins may be mediated by their pleiotropic effects. Thus, statins may modulate the function of cardiovascular cells and key signalling proteins, including small G-proteins, to ultimately exert their pleiotropic effects. Sphingosine-1-phosphate (S1P) is a naturally occurring bioactive lysophospholipid that regulates diverse physiological functions in a variety of different organ systems. Within the cardiovascular system, S1P mediates cardioprotection following ischemia/reperfusion injury, anti-inflammatory response, improvement of endothelial function, increased mobilization and differentiation of endothelial progenitor cells, inhibition of oxidation, and anti-atherogenic and anti-thrombotic actions. Early evidence suggests that the pleiotropic effects of statins may be related to an increase in S1P signalling. This review focuses on S1P signalling as the potential mechanism underlying the pleiotropic effects of statins. An improved understanding of this mechanism may be vital for establishing the clinical relevance of statins and their importance in the treatment and prevention of coronary artery disease. Key points Several studies have demonstrated a benefit from lowering serum LDL-C with statins in patients with and without clinical evidence of CAD. These may be mediated by the pleiotropic effects of statins-the mechanisms of which are incompletely understood. Early evidence suggests that statins may increase S1P signalling pathways through upregulation of the expression of S1P receptors and an increase in plasma levels of S1P to ultimately exert their pleiotropic effects. Future clinical trials and basic science research aimed at the underlying mechanisms of the pleiotropic effects of statins should enlighten us to their relative clinical relevance and importance. Mon, 04 Jul 2016 12:09:14 GMT http://hdl.handle.net/10993/27832 Title: Integration of metabolomics in heart disease and diabetes research: current achievements and future outlook. <br/> <br/>Author, co-author: Dunn, Warwick B.; Goodacre, Royston; Neyses, Ludwig; Mamas, Mamas <br/> <br/>Abstract: Metabolomics is an emerging and powerful discipline that provides an accurate and dynamic picture of the phenotype of mammalian systems through the study of endogenous and exogenous metabolites in cells, tissues, culture supernatants as well as biofluids. In the last 5 years an increase in the number of metabolomic investigations of cardiovascular diseases and diabetes has been observed. In this article the experimental strategies applied and recent examples of their application in disease and drug efficacy/toxicity biomarker detection and the employment for the discovery of new molecular pathophysiological processes related to disease onset and progression, as well as their usefulness in drug efficacy/toxicity, will be reviewed. An outlook of the requirements for future successes will also be discussed. Mon, 04 Jul 2016 12:09:04 GMT http://hdl.handle.net/10993/27831 Title: Minimising radial injury: Prevention is better than cure <br/> <br/>Author, co-author: Mamas, M. A.; Fraser, D. G.; Ratib, K.; Fath-Ordoubadi, F.; El-Omar, M.; Nolan, J.; Neyses, Ludwig <br/> <br/>Abstract: Transradial (TR) coronary intervention is associated with fewer access-site-related bleeding complications and is independently associated with a lower risk of mortality following PCI compared to procedures undertaken through the femoral route. However, recent studies that have undertaken imaging of the radial artery through the use of IVUS and OCT, as well as histological studies, suggest that TR cardiac catheterisation is associated with significant injury to the radial artery wall resulting in significant endothelial cell dysfunction. The vascular endothelium plays a central role in the regulation of vascular tone, angiogenesis and vascular remodelling through the release of vasoactive mediators in response to a variety of stimuli. Hence, trauma to the vascular endothelium and subsequent changes in endothelial cell function may contribute to patterns of injury such as intimal hyperplasia and radial artery occlusion observed following TR cardiac catheterisation. Such injury patterns to the radial artery following TR procedures may limit the success and future utility of the TR approach. Minimisation of radial artery injury should be a key procedural component of procedures undertaken through the transradial approach. © 2014, EuroPCR. All rights reserved. <br/> <br/>Commentary: cited By 9 Scopus Mon, 04 Jul 2016 12:08:48 GMT http://hdl.handle.net/10993/27829 Title: Late outcomes of drug eluting and bare metal stents in saphenous vein graft percutaneous coronary intervention. <br/> <br/>Author, co-author: Nair, Satheesh; Fath-Ordoubadi, Farzin; Clarke, Bernard; El-Omar, Magdi; Foley, James; Fraser, Doug G.; Mahadevan, Vaikom S.; Neyses, Ludwig; Khattar, Raj S.; Mamas, Mamas A. <br/> <br/>Abstract: AIMS: PCI with drug eluting stents (DES) has been shown to reduce restenosis and major adverse cardiac event (MACE) rates compared to bare metal stents (BMS) in native coronary vessels, although outcomes in saphenous vein graft (SVG) lesions are less clear. We retrospectively studied 388 consecutive patients admitted to our centre for SVG PCI to assess mortality and MACE outcomes (defined as composite endpoint of all-death, stroke, myocardial infarction, stent thrombosis and target lesion (TLR)/vessel (TVR) revascularisation) associated with BMS and DES use. METHODS AND RESULTS: Two hundred and nineteen (219) patients had BMS and 169 had DES (total 388 patients). Mean follow up was 41.9+/-23.5 months. No significant differences were observed in mortality (14.2% vs. 11.8%) or MACE (37.6% vs. 35.8%) between the BMS and DES groups at four years follow-up or at other intervening time points studied. Similarly, no differences in TVR/TLR rates were observed over a similar time period (19.8% vs. 21.6%). CONCLUSIONS: We have observed that DES and BMS use in SVG PCI have comparable mortality and MACE rates, and that in contrast to PCI in native coronary arteries, DES do not reduce revascularisation rates in our study cohort. Mon, 04 Jul 2016 12:07:55 GMT http://hdl.handle.net/10993/27828 Title: Drug eluting stents for the treatment of bare metal in-stent restenosis: long-term outcomes in real world practice. <br/> <br/>Author, co-author: Appleby, Clare E.; Khattar, Raj S.; Morgan, Kenneth; Clarke, Bernard; Curzen, Nicholas; Neyses, Ludwig; Fath-Ordoubadi, Farzin <br/> <br/>Abstract: AIMS: Drug eluting stents (DES) have had a great impact in reducing in-stent restenosis (ISR) in de novo lesions. However, long-term data regarding effectiveness and safety of these stents in treating bare metal stent (BMS) ISR are limited. We report long-term clinical outcomes in a cohort of patients with BMS-ISR treated with DES between April 2002 and December 2003 at our institution. METHODS AND RESULTS: Sixty-nine consecutive patients with significant BMS-ISR were treated with DES implantation. Sirolimus DES were used in 43 patients and paclitaxel DES in 26. All patients were followed up to determine the incidence of major adverse cardiac event (MACE) rates (all-cause death, myocardial infarction, or target vessel revascularisation [TVR]), angina class and the need for clinically driven angiography. The mean age of the cohort was 58.6 +/- 10.8 years; 68% were male, 33% were diabetic, 50% had hypertension, 78% were on statin therapy and 59% were current (19%) or previous (41%) smokers. The clinical presentation of ISR was with chronic stable angina in 54 patients, 12 had a non-ST elevation acute coronary syndrome and three presented with ST-elevation myocardial infarction. Multivessel stenting was performed in 21 patients and bifurcation stenting in seven patients. Over a mean follow period of 4.9 years, the first event MACE rate was 20% (17 events in 14 patients - eight deaths of which three were cardiac, two non-fatal myocardial infarctions and seven TVR). Excluding non-cardiac death, the adjusted MACE rate was 14.5% (12 events in 10 patients). At long-term follow-up, mean Canadian angina class decreased from 2.3 +/- 0.7 pre-procedure to 1.2 +/- 0.4, 65% of patients were angina free and 80% were free of MACE. No differences in long-term outcomes were observed between patients receiving paclitaxel and sirolimus DES. CONCLUSIONS: The use of DES for the treatment of BMS-ISR is safe and effective over a mean follow-up period of nearly five years. To our knowledge, this represents the longest follow-up data of real world patients treated in a single interventional centre. Mon, 04 Jul 2016 12:07:42 GMT http://hdl.handle.net/10993/27827 Title: ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). <br/> <br/>Author, co-author: Hamm, Christian W.; Bassand, Jean-Pierre; Agewall, Stefan; Bax, Jeroen; Boersma, Eric; Bueno, Hector; Caso, Pio; Dudek, Dariusz; Gielen, Stephan; Huber, Kurt; Ohman, Magnus; Petrie, Mark C.; Sonntag, Frank; Uva, Miguel Sousa; Storey, Robert F.; Wijns, William; Zahger, Doron Mon, 04 Jul 2016 12:07:31 GMT http://hdl.handle.net/10993/27826 Title: Resting Pd/Pa measured with intracoronary pressure wire strongly predicts fractional flow reserve. <br/> <br/>Author, co-author: Mamas, Mamas A.; Horner, Simon; Welch, Elise; Ashworth, Anthony; Millington, Simon; Fraser, Doug; Fath-Ordoubadi, Farzin; Neyses, Ludwig; El-Omar, Magdi <br/> <br/>Abstract: OBJECTIVE: To investigate the relationship between resting distal coronary pressure to aortic pressure ratio (Pd/Pa) and fractional flow reserve (FFR) obtained during maximal hyperemia. BACKGROUND: FFR is an invasive index of the functional severity of a coronary artery stenosis determined from coronary pressure measurements. It is generally believed that there is little correlation between resting Pd/Pa and FFR obtained during maximal hyperemia. We have therefore studied this relationship in a large cohort of patients who had undergone pressure- wire assessments. METHODS: 528 consecutive pressure-wire studies performed in 483 patients over a 2-year period were retrospectively analyzed. RESULTS: A linear correlation between resting Pd/Pa and FFR post-pharmacological hyperemia was observed (rho = 0.74; p < 0.0001). When a FFR of < or = 0.75 (or < or = 0.80 as per FAME) was defined as positive, a resting Pd/Pa of < or = 0.85 (< or = 0.87) had a positive predictive value (PPV) of 95% (94.6%), while a resting Pd/Pa of > or = 0.93 (> or = 0.96) had a negative predictive value (NPV) of 95.7% (93%). CONCLUSIONS: We demonstrate a strong correlation between resting Pd/Pa and FFR. Resting values of Pd/Pa can be used to predict a positive FFR result with relatively high PPV and NPV. This may potentially obviate the need for adenosine infusion in a proportion of pressure-wire studies. Mon, 04 Jul 2016 12:07:20 GMT http://hdl.handle.net/10993/27825 Title: Measurement of plasma membrane calcium-calmodulin-dependent ATPase (PMCA) activity. <br/> <br/>Author, co-author: Mohamed, Tamer M. A.; Baudoin-Stanley, Florence M.; Abou-Leisa, Riham; Cartwright, Elizabeth; Neyses, Ludwig; Oceandy, Delvac <br/> <br/>Abstract: The plasma membrane calcium-calmodulin-dependent ATPase (PMCA) is a calcium-extruding enzymatic pump that ejects calcium from the cytoplasm to the extracellular compartment. Although in excitable cells such as skeletal and cardiac muscle cells PMCA has been shown to play only a minor role in regulating global intracellular calcium concentration, increasing evidence points to an important role for PMCA in signal transduction, in particular in the nitric oxide signaling pathway. Moreover, recent evidence has shown the functional importance of PMCA in mediating cardiac contractility and vascular tone. Here we describe a method in determining PMCA activity in the microsomal membrane preparation from cultured cells that overexpress specific isoform of PMCA by using modified coupled enzyme assay. Mon, 04 Jul 2016 12:07:08 GMT http://hdl.handle.net/10993/27824 Title: Use of the Heartrail II catheter as a distal stent delivery device; an extended case series. <br/> <br/>Author, co-author: Mamas, Mamas A.; Eichhofer, Jonas; Hendry, Cara; El-Omar, Magdi; Clarke, Bernard; Neyses, Ludwig; Fath-Ordoubadi, Farzin; Fraser, Doug <br/> <br/>Abstract: AIMS: The Terumo Heartrail catheter (Terumo Corp., Tokyo, Japan) allows extra deep catheter intubation of coronary vessels and has been shown to be useful in CTO lesions. The aim of this study is to assess the safety and efficacy of using the Heartrail II catheter as a distal stent delivery system in PCI following failure of conventional techniques. METHODS AND RESULTS: We prospectively identified cases performed over a 15-month period in which a Heartrail catheter was used to facilitate stent delivery following failure of conventional techniques. Stent delivery using the Heartrail catheter was performed in 35 cases and was successful in 31 cases. Success rates of 100% in grafts, 95% in RCA, 80% in LAD and 60% in circumflex cases were recorded respectively. Successful stent delivery was associated with intubation depth, with 29/29 succeeding when the intubation depth was > 2 cm and failure in 4/5 cases when the intubation depth <or= 2 cm. There were no complications related to deep intubation of the catheter. CONCLUSIONS: Use of the Heartrail catheter is safe and highly effective for aiding stent delivery across proximal obstructions in both left and right coronary systems. The small number of unsuccessful cases were related to inability of the catheter to traverse stenotic proximal obstructions within 2 cm of the RCA and LCA origins. Mon, 04 Jul 2016 12:06:52 GMT http://hdl.handle.net/10993/27823 Title: Deletion of the intestinal plasma membrane calcium pump, isoform 1, Atp2b1, in mice is associated with decreased bone mineral density and impaired responsiveness to 1, 25-dihydroxyvitamin D3. <br/> <br/>Author, co-author: Ryan, Zachary C.; Craig, Theodore A.; Filoteo, Adelaida G.; Westendorf, Jennifer J.; Cartwright, Elizabeth J.; Neyses, Ludwig; Strehler, Emanuel E.; Kumar, Rajiv <br/> <br/>Abstract: The physiological importance of the intestinal plasma membrane calcium pump, isoform 1, (Pmca1, Atp2b1), in calcium absorption and homeostasis has not been previously demonstrated in vivo. Since global germ-line deletion of the Pmca1 in mice is associated with embryonic lethality, we selectively deleted the Pmca1 in intestinal absorptive cells. Mice with loxP sites flanking exon 2 of the Pmca1 gene (Pmca1(fl/fl)) were crossed with mice expressing Cre recombinase in the intestine under control of the villin promoter to give mice in which the Pmca1 had been deleted in the intestine (Pmca1(EKO) mice). Pmca1(EKO) mice were born at a reduced frequency and were small at the time of birth when compared to wild-type (Wt) littermates. At two months of age, Pmca1(EKO) mice fed a 0.81% calcium, 0.34% phosphorus, normal vitamin D diet had reduced whole body bone mineral density (P < 0.037), and reduced femoral bone mineral density (P < 0.015). There was a trend towards lower serum calcium and higher serum parathyroid hormone (PTH) and 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) concentrations in Pmca1(EKO) mice compared to Wt mice but the changes were not statistically significant. The urinary phosphorus/creatinine ratio was increased in Pmca1(EKO) mice (P < 0.004). Following the administration of 200 ng of 1alpha,25(OH)2D3 intraperitoneally to Wt mice, active intestinal calcium transport increased approximately 2-fold, whereas Pmca1(EKO) mice administered an equal amount of 1alpha,25(OH)2D3 failed to show an increase in active calcium transport. Deletion of the Pmca1 in the intestine is associated with reduced growth and bone mineralization, and a failure to up-regulate calcium absorption in response to 1alpha,25(OH)2D3. <br/> <br/>Commentary: Copyright (c) 2015 Elsevier Inc. All rights reserved. Mon, 04 Jul 2016 12:06:34 GMT