{"id":"https://openalex.org/W853584062","doi":null,"title":"The Role of Prenylation in Vascular Calcification","display_name":"The Role of Prenylation in Vascular Calcification","publication_year":2014,"publication_date":"2014-02-01","ids":{"openalex":"https://openalex.org/W853584062","mag":"853584062"},"language":"en","primary_location":{"id":"pmh:oai:pure.atira.dk:studenttheses/0b4aaae4-d3c8-4676-8e57-7be8106f7ce4","doi":null,"is_oa":false,"landing_page_url":"https://research.manchester.ac.uk/en/studentTheses/0b4aaae4-d3c8-4676-8e57-7be8106f7ce4","pdf_url":null,"source":{"id":"https://openalex.org/S4306400662","display_name":"Research Explorer (The University of Manchester)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I28407311","host_organization_name":"University of Manchester","host_organization_lineage":["https://openalex.org/I28407311"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"synchronisedUnifiedStudentThesis","raw_type":"Phd"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5016447131","display_name":"Arvind Ponnusamy","orcid":"https://orcid.org/0000-0002-3882-9370","observed_orcids":["https://orcid.org/0000-0002-3882-9370"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Arvind Ponnusamy","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-3882-9370","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5016447131"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10516","display_name":"Parathyroid Disorders and Treatments","score":0.9624000191688538,"subfield":{"id":"https://openalex.org/subfields/2727","display_name":"Nephrology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10516","display_name":"Parathyroid Disorders and Treatments","score":0.9624000191688538,"subfield":{"id":"https://openalex.org/subfields/2727","display_name":"Nephrology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12924","display_name":"Dermatological and Skeletal Disorders","score":0.008100000210106373,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T13453","display_name":"Alkaline Phosphatase Research Studies","score":0.007199999876320362,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/vascular-calcification","display_name":"vascular calcification","score":0.996999979019165},{"id":"https://openalex.org/keywords/prenylation","display_name":"prenylation","score":0.8880000114440918},{"id":"https://openalex.org/keywords/farnesyltransferase-inhibitors","display_name":"farnesyltransferase inhibitors","score":0.9350000023841858},{"id":"https://openalex.org/keywords/fti-277","display_name":"FTI-277","score":0.9789999723434448},{"id":"https://openalex.org/keywords/manumycin-a","display_name":"manumycin A","score":0.984000027179718},{"id":"https://openalex.org/keywords/vascular-smooth-muscle-cells","display_name":"vascular smooth muscle cells","score":0.8640000224113464},{"id":"https://openalex.org/keywords/pi3k-akt-signaling","display_name":"PI3K/Akt signaling","score":0.9779999852180481},{"id":"https://openalex.org/keywords/mineralization","display_name":"mineralization","score":0.6240000128746033},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.6759999990463257},{"id":"https://openalex.org/keywords/runx2","display_name":"Runx2","score":0.8949999809265137},{"id":"https://openalex.org/keywords/msx2","display_name":"Msx2","score":0.7879999876022339},{"id":"https://openalex.org/keywords/osteogenic-differentiation","display_name":"osteogenic differentiation","score":0.4569999873638153},{"id":"https://openalex.org/keywords/chronic-kidney-disease","display_name":"chronic kidney disease","score":0.7540000081062317},{"id":"https://openalex.org/keywords/diabetes-mellitus","display_name":"diabetes mellitus","score":0.875},{"id":"https://openalex.org/keywords/atherosclerosis","display_name":"atherosclerosis","score":0.7129999995231628}],"concepts":[{"id":"https://openalex.org/C57790582","wikidata":"https://www.wikidata.org/wiki/Q901141","display_name":"Prenylation","level":3,"score":0.8151164054870605},{"id":"https://openalex.org/C2778308172","wikidata":"https://www.wikidata.org/wiki/Q423565","display_name":"Wortmannin","level":4,"score":0.7012279629707336},{"id":"https://openalex.org/C2779395532","wikidata":"https://www.wikidata.org/wiki/Q7916469","display_name":"Vascular smooth muscle","level":3,"score":0.6851622462272644},{"id":"https://openalex.org/C2776990775","wikidata":"https://www.wikidata.org/wiki/Q2699676","display_name":"Farnesyl pyrophosphate","level":4,"score":0.6268268823623657},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.5707255601882935},{"id":"https://openalex.org/C2780309369","wikidata":"https://www.wikidata.org/wiki/Q933382","display_name":"Calcification","level":2,"score":0.5631369948387146},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.5266081094741821},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4837672710418701},{"id":"https://openalex.org/C2776415932","wikidata":"https://www.wikidata.org/wiki/Q48743","display_name":"Western blot","level":3,"score":0.4493659734725952},{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.38569706678390503},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3840175271034241},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.38048332929611206},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.37811344861984253},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.37309789657592773},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.37090161442756653},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.24373823404312134},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.2435164749622345},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.09457486867904663},{"id":"https://openalex.org/C112243037","wikidata":"https://www.wikidata.org/wiki/Q22327117","display_name":"ATP synthase","level":3,"score":0.09230202436447144},{"id":"https://openalex.org/C2992686903","wikidata":"https://www.wikidata.org/wiki/Q208453","display_name":"Smooth muscle","level":2,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:pure.atira.dk:studenttheses/0b4aaae4-d3c8-4676-8e57-7be8106f7ce4","doi":null,"is_oa":false,"landing_page_url":"https://research.manchester.ac.uk/en/studentTheses/0b4aaae4-d3c8-4676-8e57-7be8106f7ce4","pdf_url":null,"source":{"id":"https://openalex.org/S4306400662","display_name":"Research Explorer (The University of Manchester)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I28407311","host_organization_name":"University of Manchester","host_organization_lineage":["https://openalex.org/I28407311"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"synchronisedUnifiedStudentThesis","raw_type":"Phd"},{"id":"mag:853584062","doi":null,"is_oa":false,"landing_page_url":"http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.617990","pdf_url":null,"source":{"id":"https://openalex.org/S4306532719","display_name":"[Thesis]. Manchester, UK: The University of                    Manchester; 2014.","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":"[Thesis]. Manchester, UK: The University of Manchester; 2014.","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9940000176429749,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":142,"referenced_works":["https://openalex.org/W1536684769","https://openalex.org/W1558058709","https://openalex.org/W1562863690","https://openalex.org/W1563363743","https://openalex.org/W1566737177","https://openalex.org/W1594384581","https://openalex.org/W1617532721","https://openalex.org/W1824220821","https://openalex.org/W1864862165","https://openalex.org/W1899123775","https://openalex.org/W1907050532","https://openalex.org/W1963547997","https://openalex.org/W1964551999","https://openalex.org/W1966856123","https://openalex.org/W1967402039","https://openalex.org/W1969161473","https://openalex.org/W1970468800","https://openalex.org/W1970882491","https://openalex.org/W1971339165","https://openalex.org/W1973895552","https://openalex.org/W1975449649","https://openalex.org/W1977825023","https://openalex.org/W1978478799","https://openalex.org/W1979595420","https://openalex.org/W1980918720","https://openalex.org/W1982718573","https://openalex.org/W1983345831","https://openalex.org/W1986415554","https://openalex.org/W1990355228","https://openalex.org/W1990750680","https://openalex.org/W1991287545","https://openalex.org/W1993216157","https://openalex.org/W1994596418","https://openalex.org/W1994926193","https://openalex.org/W1997052574","https://openalex.org/W1997611649","https://openalex.org/W1998833474","https://openalex.org/W1999701259","https://openalex.org/W2004200901","https://openalex.org/W2008470915","https://openalex.org/W2013009411","https://openalex.org/W2014622351","https://openalex.org/W2016637403","https://openalex.org/W2021120405","https://openalex.org/W2021128415","https://openalex.org/W2025589168","https://openalex.org/W2030273291","https://openalex.org/W2031471867","https://openalex.org/W2033778242","https://openalex.org/W2037243061","https://openalex.org/W2039953525","https://openalex.org/W2040196938","https://openalex.org/W2040663849","https://openalex.org/W2042256973","https://openalex.org/W2042262392","https://openalex.org/W2042670807","https://openalex.org/W2043395027","https://openalex.org/W2045733357","https://openalex.org/W2048996725","https://openalex.org/W2049186397","https://openalex.org/W2049212536","https://openalex.org/W2050277287","https://openalex.org/W2051655894","https://openalex.org/W2052333525","https://openalex.org/W2053907246","https://openalex.org/W2054658759","https://openalex.org/W2058138221","https://openalex.org/W2061234826","https://openalex.org/W2066118482","https://openalex.org/W2067829686","https://openalex.org/W2068700160","https://openalex.org/W2070707732","https://openalex.org/W2072327228","https://openalex.org/W2079111418","https://openalex.org/W2080281663","https://openalex.org/W2081065174","https://openalex.org/W2082925412","https://openalex.org/W2083695927","https://openalex.org/W2084789695","https://openalex.org/W2085845962","https://openalex.org/W2085921220","https://openalex.org/W2087387262","https://openalex.org/W2087899522","https://openalex.org/W2089642031","https://openalex.org/W2089750661","https://openalex.org/W2092214723","https://openalex.org/W2092921933","https://openalex.org/W2096024580","https://openalex.org/W2096238248","https://openalex.org/W2096806896","https://openalex.org/W2100918102","https://openalex.org/W2101301592","https://openalex.org/W2104042512","https://openalex.org/W2104127478","https://openalex.org/W2105779783","https://openalex.org/W2108958930","https://openalex.org/W2111193333","https://openalex.org/W2111778006","https://openalex.org/W2113932898","https://openalex.org/W2114114824","https://openalex.org/W2120004009","https://openalex.org/W2120129493","https://openalex.org/W2123740493","https://openalex.org/W2124364682","https://openalex.org/W2124591820","https://openalex.org/W2127256519","https://openalex.org/W2129651548","https://openalex.org/W2130835350","https://openalex.org/W2132029924","https://openalex.org/W2133362776","https://openalex.org/W2134120087","https://openalex.org/W2134275717","https://openalex.org/W2136324267","https://openalex.org/W2137035181","https://openalex.org/W2139193176","https://openalex.org/W2139709244","https://openalex.org/W2139999965","https://openalex.org/W2146662079","https://openalex.org/W2147114673","https://openalex.org/W2147700211","https://openalex.org/W2147834547","https://openalex.org/W2148413329","https://openalex.org/W2148618665","https://openalex.org/W2150762378","https://openalex.org/W2153201206","https://openalex.org/W2153484361","https://openalex.org/W2155188161","https://openalex.org/W2156516895","https://openalex.org/W2160022618","https://openalex.org/W2160553642","https://openalex.org/W2161221839","https://openalex.org/W2165639753","https://openalex.org/W2165853103","https://openalex.org/W2170967285","https://openalex.org/W2171830717","https://openalex.org/W2173344695","https://openalex.org/W2176744910","https://openalex.org/W2178557511","https://openalex.org/W2185760978","https://openalex.org/W2316903752","https://openalex.org/W2326831456","https://openalex.org/W2329074064"],"related_works":["https://openalex.org/W2312664918","https://openalex.org/W2799805941","https://openalex.org/W4384521904","https://openalex.org/W2730881034","https://openalex.org/W2165853103","https://openalex.org/W4409098350","https://openalex.org/W4399040323","https://openalex.org/W2070932256","https://openalex.org/W2048635866","https://openalex.org/W4292547790"],"abstract_inverted_index":{"Vascular":[0],"calcification":[1,48,64,116,143],"is":[2,24,40],"an":[3,328],"active,":[4],"regulated":[5],"process":[6],"in":[7,121,124,134,146,153,187,203,221,392,430],"which":[8,39,78,125],"vascular":[9,47,63,115,480],"smooth":[10],"muscle":[11,324],"cells":[12,17,71],"(VSMCs)":[13],"differentiate":[14],"into":[15],"osteoblast-like":[16],"and":[18,33,49,75,84,92,111,149,156,173,180,296,308,321,348,353,384,424,457],"deposit":[19,130],"a":[20,118,131,154,471],"mineralised":[21,132],"matrix.":[22],"It":[23],"well":[25,119],"established":[26],"that":[27,59,177,194,254,336,439,464],"patients":[28],"with":[29,275,346,452],"chronic":[30],"kidney":[31],"disease":[32,352,456],"diabetes":[34],"have":[35],"poor":[36],"cardiovascular":[37],"outcomes":[38],"thought":[41],"to":[42,45,102,129,219,419],"be":[43,260,470],"due":[44],"increased":[46,200,385,399],"atherosclerosis.":[50],"Previous":[51],"work":[52],"from":[53,344,450],"the":[54,82,95,104,135,222,243,255,358,431,477],"host":[55],"laboratory":[56],"has":[57],"shown":[58],"nitrogen-containing":[60],"bisphosphonates":[61],"attenuate":[62],"by":[65,212,251,265,282],"inhibiting":[66],"farnesyl":[67,73,107],"pyrophosphate":[68,74,77],"synthase,":[69],"depleting":[70],"of":[72,86,98,106,137,144,224,246,257,273,292,341,360,397,427,433,447,479],"geranylgeranyl":[76],"are":[79,127],"essential":[80],"for":[81,476],"prenylation":[83],"activation":[85,186,383],"small":[87],"GTPases":[88],"such":[89],"as":[90],"Ras":[91,170,184,363,381,407,467],"Rho.":[93],"Therefore,":[94],"initial":[96],"aim":[97],"this":[99,150,167],"study":[100,462],"was":[101,333,372],"determine":[103,207,357],"effects":[105,256,359],"transferase":[108],"inhibitors":[109],"(FTI-277":[110],"manumycin":[112,161,181,198],"A)":[113],"on":[114,166,248,365,406,410],"using":[117],"validated":[120],"vitro":[122,147],"model":[123],"VSMCs":[126,145,216,274,429],"induced":[128,218,445],"matrix":[133,315],"presence":[136,223],"?-glycerophosphate.":[138],"\tFTI-277":[139],"significantly":[140,278,288],"inhibited":[141,210,289,303,377,389,443],"?-glycerophosphate-induced":[142,304],"(p<0.001),":[148,379,401],"inhibition":[151,364,478],"occurred":[152],"dose-":[155],"time-dependent":[157],"manner.":[158],"In":[159,285],"contrast,":[160],"A":[162,182],"had":[163,403],"no":[164,404],"effect":[165,245,405],"process.":[168],"Active":[169],"pull-down":[171],"assays":[172],"western":[174],"blotting":[175],"confirmed":[176],"both":[178],"FTI-277":[179,209,225,247,258,287,301,337],"decreased":[183,242,380],"GTPase":[185,382],"VSMCs.":[188],"Western":[189],"blot":[190],"analysis":[191],"also":[192,302,334,417],"showed":[193],"FTI-277,":[195],"but":[196,388,402],"not":[197],"A,":[199],"Akt":[201,234,270,386,411],"phosphorylation":[202,387,391],"these":[204],"cells.":[205],"To":[206],"whether":[208],"mineralisation":[211,340,378,400,446],"promoting":[213],"PI3K/Akt":[214],"signalling,":[215],"were":[217],"mineralise":[220],"plus":[226],"either":[227],"wortmannin":[228,276],"(a":[229],"PI3K":[230,268],"inhibitor),":[231],"SH6":[232],"(an":[233],"inhibitor)":[235],"or":[236,269,409,412,466],"vehicle":[237],"alone.":[238],"These":[240],"reagents":[241],"inhibitory":[244],"mineral":[249,280],"deposition":[250,281],"VSMCs,":[252],"demonstrating":[253],"can":[259],"negated,":[261],"at":[262],"least":[263],"partially,":[264],"preventing":[266],"downstream":[267],"signalling.":[271],"Incubation":[272],"alone":[277],"promoted":[279,314],"VSMC":[283,294,299,366,422],"(p<0.001).":[284],"addition,":[286],"phosphate-induced":[290,339],"apoptosis":[291,426],"human":[293,428],"(p<0.05),":[295,313,320],"prevented":[297],"PDGF-induced":[298,421],"migration.":[300],"Runx2,":[305],"Msx":[306],"2":[307],"alkaline":[309],"phosphatase":[310],"mRNA":[311,318],"expression":[312,319],"Gla":[316],"protein":[317],"maintained":[322],"?-smooth":[323],"actin":[325],"expression.":[326],"Using":[327],"ex":[329],"vivo":[330,436],"assay,":[331],"it":[332],"demonstrated":[335,438],"inhibits":[338],"aortic":[342,448],"rings":[343,449],"rats":[345,451],"early":[347],"end":[349,453],"stage":[350,454],"renal":[351,455],"sham-operated":[354,458],"controls.":[355,459],"\tTo":[356],"more":[361],"specific":[362],"mineralisation,":[367],"Farnesyl":[368],"Thiosalicylic":[369],"Acid":[370],"(FTS)":[371],"used.":[373],"FTS":[374,398,416,440],"(40":[375,441],"\ufffdM)":[376,442],"Erk":[390,413],"vitro.":[393],"However":[394],"lower":[395],"doses":[396],"activation,":[408],"phosphorylation.":[414],"appeared":[418],"delay":[420],"migration":[423],"induce":[425],"absence":[432],"serum.":[434],"Ex":[435],"studies":[437],"phosphate":[444],"This":[461],"demonstrates":[463],"farnesylation,":[465],"specifically,":[468],"could":[469],"potential":[472],"novel":[473],"therapeutic":[474],"target":[475],"calcification.":[481]},"counts_by_year":[],"updated_date":"2025-10-10T17:16:08.811792","created_date":"2016-06-24T00:00:00"}
