X. Hou, N. Appleby, Tania I. Fuentes, L. Longo, L. Bailey, N. Hasaniya, M. Kearns-Jonker
{"title":"Isolation, Characterization, and Spatial Distribution of Cardiac Progenitor Cells in the Sheep Heart.","authors":"X. Hou, N. Appleby, Tania I. Fuentes, L. Longo, L. Bailey, N. Hasaniya, M. Kearns-Jonker","doi":"10.4172/2155-9880.S6-004","DOIUrl":"https://doi.org/10.4172/2155-9880.S6-004","url":null,"abstract":"BACKGROUND Laboratory large animal models are important for establishing the efficacy of stem cell therapies that may be translated into clinical use. The similarity of ovine and human cardiovascular systems provides an opportunity to use the sheep as a large animal model in which to optimize cell-based treatments for the heart. Recent clinical trials in humans using endogenous cardiovascular progenitor cells report significant improvement in cardiac function following stem cell-based therapy. To date, however, endogenous cardiovascular progenitor cells have not been isolated from the sheep heart. METHODS Cardiovascular cells expressing SSEA-4, CD105 and c-kit were isolated by flow cytometry and cloned from the right atrium of neonatal sheep. The expression of GATA-4, c-kit, and Isl1 was identified by PCR in the cloned cells. Immunohistochemical staining was used to compare the number of SSEA-4 positive cells in the right auricle, right atrium, left ventricle and the apex of the heart of fetal, neonatal and adult sheep. The number of SSEA4+cells was also compared in fetal, pregnant and non-pregnant adult sheep. RESULTS Four distinct cardiac progenitor cell sub-populations were identified in sheep, including CD105+SSEA-4+c-kit+Isl1+GATA-4+cells, CD105+SSEA-4+c-kit+Isl1+GATA-4-cells, CD105+SSEA-4-c-kit-Isl1+GATA-4-cells, and CD105+SSEA-4-c-kit+Isl1+GATA-4-cells. Immunohistochemical staining for SSEA-4 showed that labeled cells were most abundant in the right atrium of fetal hearts where niches of progenitor cells could be identified. CONCLUSION We determined the phenotype and distribution of cardiac progenitor cells in the sheep heart. The availability of cloned endogenous cardiac progenitor cells from sheep will provide a valuable resource for optimizing the conditions for cardiac repair in the ovine model.","PeriodicalId":89581,"journal":{"name":"Journal of clinical & experimental cardiology","volume":"S6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70323492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Geeta Datta, Himanshu Gupta, Zhenghao Zhang, Palgunachari Mayakonda, G M Anantharamaiah, C Roger White
{"title":"HDL Mimetic Peptide Administration Improves Left Ventricular Filling and Cardiac output in Lipopolysaccharide-Treated Rats.","authors":"Geeta Datta, Himanshu Gupta, Zhenghao Zhang, Palgunachari Mayakonda, G M Anantharamaiah, C Roger White","doi":"10.4172/2155-9880.1000172","DOIUrl":"10.4172/2155-9880.1000172","url":null,"abstract":"<p><p>AIMS: Cardiac dysfunction is a complication of sepsis and contributes to morbidity and mortality. Since raising plasma apolipoprotein (apo) A-I and high density lipoprotein (HDL) concentration reduces sepsis complications, we tested the hypothesis that the apoA-I mimetic peptide 4F confers similar protective effects in rats treated with lipopolysaccharide (LPS). METHODS AND RESULTS: Male Sprague-Dawley (SD) rats were randomized to receive saline vehicle (n=13), LPS (10 mg/kg: n=16) or LPS plus 4F (10 mg/kg each: n=13) by intraperitoneal injection. Plasma cytokine and chemokine levels were significantly elevated 24 hrs after LPS administration. Echocardiographic studies revealed changes in cardiac dimensions that resulted in a reduction in left ventricular end-diastolic volume (LVEDV), stroke volume (SV) and cardiac output (CO) 24 hrs after LPS administration. 4F treatment reduced plasma levels of inflammatory mediators and increased LV filling, resulting in improved cardiac performance. Chromatographic separation of lipoproteins from plasma of vehicle, LPS and LPS+4F rats revealed similar profiles. Further analyses showed that LPS treatment reduced the agarose electrophoretic mobility of isolated HDL fractions. HDL-associated proteins were characterized by SDSPAGE and mass spectrometry. ApoA-I and apoA-IV were reduced while apoE content was increased in LPStreated rats. 4F treatment in vivo attenuated changes in HDL-associated apolipoproteins and increased the electrophoretic mobility of the particle. CONCLUSIONS: The ability of 4F to reduce inflammation and improve cardiac performance in LPS-treated rats may be due to its capacity to neutralize endotoxin and prevent adverse changes in HDL composition and function.</p>","PeriodicalId":89581,"journal":{"name":"Journal of clinical & experimental cardiology","volume":"2 172","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514969/pdf/nihms363777.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31111929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mostafa El-Refai, Olesya Krivospitskaya, Edward L Peterson, Karen Wells, L Keoki Williams, David E Lanfear
{"title":"Relationship of Loop Diuretic Dosing and Acute Changes in Renal Function during Hospitalization for Heart Failure.","authors":"Mostafa El-Refai, Olesya Krivospitskaya, Edward L Peterson, Karen Wells, L Keoki Williams, David E Lanfear","doi":"10.4172/2155-9880.1000164","DOIUrl":"https://doi.org/10.4172/2155-9880.1000164","url":null,"abstract":"<p><strong>Background: </strong>Worsening renal function (WRF) during heart failure (HF) hospitalization is an accepted correlate of poor prognosis. Loop diuretics are increasingly being considered as a potential cause of worsened HF outcomes, perhaps via WRF. However, the magnitude of worsening in renal function attributable to loop diuretics has not been quantified.</p><p><strong>Methods: </strong>This was a retrospective cohort study of patients who received care from a large health system and had a primary hospital discharge diagnosis of HF between Jan 1, 2000 and June 30, 2008. Patients with preexisting end-stage renal disease were excluded. Daily creatinine (Cr) measurements, furosemide dosing (only loop diuretic on hospital formulary), and radiocontrast dye studies were collected using administrative data. Day-to-day changes in Cr and MDRD estimated glomerular filtration (eGFR) were calculated. The first Cr or eGFR value during hospitalization or in the emergency department was considered baseline. Generalized estimating equations were used to test the association furosemide exposure over previous 2 days to the daily change in Cr and eGFR. Covariates included undergoing radiocontrast study, age, race, gender, and baseline Cr or eGFR.</p><p><strong>Results: </strong>Among 6071 patients who met inclusion criteria there were a total of 20,645 observations. This cohort was 51% female, 68% African American, and baseline Cr was 1.36 mg/dl. Furosemide exposure was associated with an average daily increase in Cr of 0.021 mg/dL and decrease in eGFR of 0.72 ml/min/1.73m2 (per 100 mg furosemide daily, both p<0.001). Over a typical length of stay of 5 days this would amount to a Cr increase of 0.11 mg/dL or decrease in eGFR of 3.6 ml/min/1.73m<sup>2</sup>. Furosemide exposure accounted for only 0.4% and 0.1% of the variation in Cr and eGFR changes, respectively. Undergoing radiocontrast study, African American race, and higher age were associated with day-to-day creatinine increases (all p<0.01). Reanaysis after classifying furosemide exposure into low (<40mg/day), medium (40-100mg/day), and high (>100mg/day) and censoring patients-days after radiocontrast exposure did not significantly affect the magnitude of the worsening renal function.</p><p><strong>Conclusions: </strong>While loop diuretic exposure is statistically associated with WRF among hospitalized HF patients, the associated magnitude of renal function change is very small, and loop diuretics explain little of the variability in renal function during hospitalization. More important explanatory factors likely exist but remain unidentified.</p>","PeriodicalId":89581,"journal":{"name":"Journal of clinical & experimental cardiology","volume":"2 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593064/pdf/nihms341772.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31300061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John F Carlquist, Jason T McKinney, Benjamin D Horne, Nicola J Camp, Lisa Cannon-Albright, Joseph B Muhlestein, Paul Hopkins, Jessica L Clarke, Chrissa P Mower, James J Park, Zachary P Nicholas, John A Huntinghouse, Jeffrey L Anderson
{"title":"Common Variants in 6 Lipid-Related Genes Discovered by High-Resolution DNA Melting Analysis and Their Association with Plasma Lipids.","authors":"John F Carlquist, Jason T McKinney, Benjamin D Horne, Nicola J Camp, Lisa Cannon-Albright, Joseph B Muhlestein, Paul Hopkins, Jessica L Clarke, Chrissa P Mower, James J Park, Zachary P Nicholas, John A Huntinghouse, Jeffrey L Anderson","doi":"10.4172/2155-9880.1000138","DOIUrl":"https://doi.org/10.4172/2155-9880.1000138","url":null,"abstract":"<p><p>BACKGROUND: Total cholesterol was among the earliest identified risk factors for coronary heart disease (CHD). We sought to identify genetic variants in six genes associated with lipid metabolism and estimate their respective contribution to risk for CHD. METHODS: For 6 lipid-associated genes (LCAT, CETP, LIPC, LPL, SCARB1, and ApoF) we scanned exons, 5' and 3' untranslated regions, and donor and acceptor splice sites for variants using Hi-Res Melting® curve analysis (HRMCA) with confirmation by cycle sequencing. Healthy subjects were used for SNP discovery (n=64), haplotype determination/tagging SNP discovery (n=339), and lipid association testing (n=786). RESULTS: In 17,840 bases of interrogated sequence, 90 variant SNPs were identified; 19 (21.1%) previously unreported. Thirty-four variants (37.8%) were exonic(16 non-synonymous), 28 (31.1%) in intron-exon boundaries, and 28 (31.1%) in the 5' and 3' untranslated regions. Compared to cycle sequencing, HRMCA had sensitivity of 99.4% and specificity of 97.7%. Tagging SNPs (n=38) explained >90% of the variation in the 6 genes and identified linkage disequilibrium (LD) groups. Significant beneficial lipid profiles were observed for CETP LD group 2, LIPC LD groups 1 and 7, and SCARB1 LD groups 1, 3 and 4. Risk profiles worsened for CETP LD group 3, LPL LD group 4. CONCLUSIONS: These findings demonstrate the feasibility, sensitivity, and specificity of HRMCA for SNP discovery. Variants identified in these genes may be used to predict lipid-associated risk and reclassification of clinical CHD risk.</p>","PeriodicalId":89581,"journal":{"name":"Journal of clinical & experimental cardiology","volume":"2 138","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251308/pdf/nihms-313383.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30373441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georgeta Mihai, Xin He, Xiaolan Zhang, Beth McCarthy, Tam Tran, Michael Pennell, Jessica Blank, Orlando P Simonetti, Rebecca D Jackson, Subha V Raman
{"title":"Design and Rationale for the Study of Changes in Iron and Atherosclerosis Risk in Perimenopause.","authors":"Georgeta Mihai, Xin He, Xiaolan Zhang, Beth McCarthy, Tam Tran, Michael Pennell, Jessica Blank, Orlando P Simonetti, Rebecca D Jackson, Subha V Raman","doi":"10.4172/2155-9880.1000152","DOIUrl":"https://doi.org/10.4172/2155-9880.1000152","url":null,"abstract":"<p><p>This study seeks to investigate changes in iron homeostasis and carotid arteries in women at risk of atherosclerosis, addressing a relatively unexplored hypothesis explaining why women have a 5-10 year lag in initial atherosclerotic events. Recent evidence points to hepcidin, the key regulator of macrophage iron uptake and release, as a potential mediator of risk. Furthermore, iron catalyzes the generation of free radicals that oxidize cholesterol stimulating atheroma formation. Magnetic resonance imaging (MRI) is ideally suited to study iron because of iron's local effects on magnetic susceptibility that can be quantified using a relaxation parameter called T2* ('T2-star'), as well as the ability to noninvasively characterize and quantify atherosclerotic plaque with MRI. This work outlines the rationale and study design to provide critical evidence related to the iron hypothesis, such that novel diagnostics and therapeutics to attenuate risk may be derived from a better understanding of iron's role in atherosclerosis.</p>","PeriodicalId":89581,"journal":{"name":"Journal of clinical & experimental cardiology","volume":"2 ","pages":"152"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279750/pdf/nihms352850.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30472184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}