2024
A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease
van Dyck C, Mecca A, O’Dell R, Bartlett H, Diepenbrock N, Huang Y, Hamby M, Grundman M, Catalano S, Caggiano A, Carson R. A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 20. PMID: 38273408, PMCID: PMC10809445, DOI: 10.1186/s13195-024-01382-2.Peer-Reviewed Original ResearchConceptsMild to moderate dementiaPositron emission tomographyAlzheimer's diseaseVolumetric MRIModerate dementiaClinical rating scalesSynaptic vesicle glycoprotein 2ACerebrospinal fluidMouse model of ADPharmacodynamic effectsPlacebo-controlled phase 1 clinical trialBiomarkers of AD pathologyClinical trialsCognitive measuresNominally significant differencesPhase 1 clinical trialModel of ADHippocampal cortexPhase 1/2 studyRating ScaleParallel-group trialSynaptic densityTrial registrationThe clinical trialPlacebo-controlledSigma-2 receptor ligands
2014
The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke
Joseph JP, Mecca AP, Regenhardt RW, Bennion DM, Rodríguez V, Desland F, Patel NA, Pioquinto DJ, Unger T, Katovich MJ, Steckelings UM, Sumners C. The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke. Neuropharmacology 2014, 81: 134-141. PMID: 24508710, PMCID: PMC7472595, DOI: 10.1016/j.neuropharm.2014.01.044.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin II Type 2 Receptor BlockersAnimalsBrain InfarctionBrain IschemiaCD11b AntigenCerebrovascular CirculationCytokinesDisease Models, AnimalDose-Response Relationship, DrugEndothelin-1Glial Fibrillary Acidic ProteinImidazolesMaleNitric Oxide Synthase Type IIPeroxidasePyridinesRatsRats, Sprague-DawleyStrokeSulfonamidesThiophenesTime FactorsConceptsMiddle cerebral artery occlusionPost-stroke administrationEndothelin-1Neurological deficitsIschemic strokeCerebroprotective actionCerebral damageCerebral ischemiaAT2R agonistChemokine (C-C) motif ligand 2Inducible nitric oxide synthaseBeneficial effectsCerebral infarct sizeMCAO-induced increaseCerebral artery occlusionAnti-inflammatory effectsCerebral blood flowNitric oxide synthaseSelective AT2R agonistPotential therapeutic valueType 2 mRNAAT2R inhibitorArtery occlusionPeripheral administrationHemorrhagic stroke
2013
Centrally administered angiotensin‐(1–7) increases the survival of stroke‐prone spontaneously hypertensive rats
Regenhardt RW, Mecca AP, Desland F, Ritucci‐Chinni P, Ludin JA, Greenstein D, Banuelos C, Bizon JL, Reinhard MK, Sumners C. Centrally administered angiotensin‐(1–7) increases the survival of stroke‐prone spontaneously hypertensive rats. Quarterly Journal Of Experimental Physiology And Cognate Medical Sciences 2013, 99: 442-453. PMID: 24142453, PMCID: PMC7416533, DOI: 10.1113/expphysiol.2013.075242.Peer-Reviewed Original ResearchConceptsHaemorrhagic strokeHypertensive ratsMicroglial activationIschemic strokeNeurological statusTherapeutic targetBeneficial actionsInfusion of AngMas receptor blockerHigh sodium dietPotential new therapeutic targetAction of angiotensinNumber of microgliaMechanism of injuryNumber of hemorrhagesSerum corticosterone levelsActivation of angiotensinPotential therapeutic targetNew therapeutic targetsPotential beneficial actionsPotential beneficial roleDays of ageAng-(1-7) treatmentIntracerebral inflammationMicroglial numbersAnti-inflammatory effects of angiotensin-(1-7) in ischemic stroke
Regenhardt RW, Desland F, Mecca AP, Pioquinto DJ, Afzal A, Mocco J, Sumners C. Anti-inflammatory effects of angiotensin-(1-7) in ischemic stroke. Neuropharmacology 2013, 71: 154-163. PMID: 23583926, PMCID: PMC3664115, DOI: 10.1016/j.neuropharm.2013.03.025.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IAnimalsAnti-Inflammatory Agents, Non-SteroidalBrain IschemiaCells, CulturedCerebral CortexDisease Models, AnimalGene Expression RegulationMaleMiceMice, Inbred StrainsMice, KnockoutMicrogliaNerve Tissue ProteinsNeuroprotective AgentsNitric OxideNitric Oxide Synthase Type IIPeptide FragmentsProto-Oncogene MasProto-Oncogene ProteinsRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledSpecific Pathogen-Free OrganismsStrokeConceptsInducible nitric oxide synthaseAnti-inflammatory effectsIschemic strokeEndothelin-1Cerebral cortexMiddle cerebral artery occlusionCerebral infarct sizeDifferentiation molecule 11bIntracerebral inflammatory responseCerebral artery occlusionAnti-inflammatory actionLipopolysaccharide-induced increasePro-inflammatory cytokinesCerebral blood flowINOS protein expressionNitric oxide synthaseNitric oxide productionNitric oxide generationExpression of mRNAAng-(1-7) treatmentSignificant cerebroprotectionCerebral vasoconstrictionArtery occlusionCerebroprotective actionReceptor MasUtilizing a cranial window to visualize the middle cerebral artery during endothelin-1 induced middle cerebral artery occlusion.
Regenhardt RW, Ansari S, Azari H, Caldwell KJ, Mecca AP. Utilizing a cranial window to visualize the middle cerebral artery during endothelin-1 induced middle cerebral artery occlusion. Journal Of Visualized Experiments 2013, e50015. PMID: 23463164, PMCID: PMC3605805, DOI: 10.3791/50015.Peer-Reviewed Original ResearchConceptsCranial windowEndothelin-1Cerebral arteryBrain parenchymaMiddle cerebral artery occlusion modelMiddle cerebral artery occlusionCerebral artery occlusionArtery occlusion modelMiddle cerebral arteryArtery occlusionIschemic strokeVasoconstricting peptideOcclusion modelVisualized vesselsLateral aspectTemporal boneArteryProximal portionRat cerebrumDuraVessel diameterCortical surfaceMCAOParietal boneParenchymaEndothelin-1 induced middle cerebral artery occlusion model for ischemic stroke with laser Doppler flowmetry guidance in rat.
Ansari S, Azari H, Caldwell KJ, Regenhardt RW, Hedna VS, Waters MF, Hoh BL, Mecca AP. Endothelin-1 induced middle cerebral artery occlusion model for ischemic stroke with laser Doppler flowmetry guidance in rat. Journal Of Visualized Experiments 2013 PMID: 23438950, PMCID: PMC3601209, DOI: 10.3791/50014.Peer-Reviewed Original ResearchConceptsEndothelin-1Laser Doppler flowmetryCerebral ischemiaIschemic strokeHuman strokeMiddle cerebral artery occlusion modelMiddle cerebral artery areaET-1 modelArtery occlusion modelET-1 infusionFocal cerebral ischemiaCause of deathDuration of occlusionNumber one causeArtery constrictionPartial reperfusionReperfusion ratesIschemic damageMCAO modelStereotaxic injectionArtery areaStroke volumeDoppler flowmetryExtracranial vesselsOcclusion model
2011
Cerebroprotection by angiotensin‐(1–7) in endothelin‐1‐induced ischaemic stroke
Mecca AP, Regenhardt RW, O’Connor T, Joseph JP, Raizada MK, Katovich MJ, Sumners C. Cerebroprotection by angiotensin‐(1–7) in endothelin‐1‐induced ischaemic stroke. Quarterly Journal Of Experimental Physiology And Cognate Medical Sciences 2011, 96: 1084-1096. PMID: 21685445, PMCID: PMC3210510, DOI: 10.1113/expphysiol.2011.058578.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IAngiotensin IIAngiotensin-Converting Enzyme 2AnimalsDiminazeneEndothelin-1Enzyme ActivationInfarction, Middle Cerebral ArteryMaleNitric Oxide Synthase Type IIPeptide FragmentsPeptidyl-Dipeptidase AProto-Oncogene MasProto-Oncogene ProteinsRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledStrokeConceptsMiddle cerebral artery occlusionIschemic strokeDiminazine aceturateNeurological deficitsBeneficial actionsInducible nitric oxide synthase (iNOS) expressionInducible nitric oxide synthase (iNOS) mRNA expressionNitric oxide synthase mRNA expressionNitric oxide synthase expressionCerebral infarct sizeCerebral artery occlusionCerebral ischemic strokeOxide synthase expressionCerebral blood flowExert beneficial actionsType 1 receptorActivation of angiotensinSynthase mRNA expressionACE2 activatorACE2-AngCerebroprotective propertiesDIZE treatmentCerebral infarctsProduction of angiotensinArtery occlusion
2010
Halogenated aromatic amino acid 3,5-dibromo-d-tyrosine produces beneficial effects in experimental stroke and seizures
Cao W, Glushakov A, Shah HP, Mecca AP, Sumners C, Shi P, Seubert CN, Martynyuk AE. Halogenated aromatic amino acid 3,5-dibromo-d-tyrosine produces beneficial effects in experimental stroke and seizures. Amino Acids 2010, 40: 1151-1158. PMID: 20839013, PMCID: PMC8396070, DOI: 10.1007/s00726-010-0739-4.Peer-Reviewed Original ResearchConceptsMiddle cerebral artery occlusionET-1 administrationInfarct volumePTZ administrationEndothelin-1Cardiovascular parametersOnset of MCAOCerebral artery occlusionArterial blood pressureCaspase-3-positive cellsSpontaneous locomotor activityNovel therapeutic directionArtery occlusionExperimental strokeNeurological deficitsBlood pressureSeizure scoreNeurological functionIntracerebral injectionIntraperitoneal injectionBolus injectionRat modelHeart rateControl animalsPositive cells
2009
Therapeutic Implications of the Vasoprotective Axis of the Renin-Angiotensin System in Cardiovascular Diseases
Ferreira AJ, Santos RA, Bradford CN, Mecca AP, Sumners C, Katovich MJ, Raizada MK. Therapeutic Implications of the Vasoprotective Axis of the Renin-Angiotensin System in Cardiovascular Diseases. Hypertension 2009, 55: 207-213. PMID: 20038757, PMCID: PMC2826213, DOI: 10.1161/hypertensionaha.109.140145.Peer-Reviewed Original ResearchEfficacy of 3,5‐dibromo‐L‐phenylalanine in rat models of stroke, seizures and sensorimotor gating deficit
Cao W, Shah H, Glushakov A, Mecca A, Shi P, Sumners C, Seubert C, Martynyuk A. Efficacy of 3,5‐dibromo‐L‐phenylalanine in rat models of stroke, seizures and sensorimotor gating deficit. British Journal Of Pharmacology 2009, 158: 2005-2013. PMID: 20050189, PMCID: PMC2807662, DOI: 10.1111/j.1476-5381.2009.00498.x.Peer-Reviewed Original ResearchConceptsSensorimotor gating deficitsEndothelin-1Prepulse inhibitionMK-801Rat modelGating deficitsN-methyl-D-aspartate (NMDA) receptor antagonist dizocilpineDisruption of PPINeuropsychiatric disordersSelective glutamate receptor antagonistsArterial blood pressureMiddle cerebral arteryGlutamate receptor antagonistsSerious side effectsFurther clinical developmentPentylenetetrazole injectionBlood pressureCerebral arteryGlutamatergic activityGlutamatergic agentsIntracerebral injectionReceptor antagonistBrain damageBrain injuryNMDA antagonistsCandesartan pretreatment is cerebroprotective in a rat model of endothelin‐1‐induced middle cerebral artery occlusion
Mecca AP, O'Connor TE, Katovich MJ, Sumners C. Candesartan pretreatment is cerebroprotective in a rat model of endothelin‐1‐induced middle cerebral artery occlusion. Quarterly Journal Of Experimental Physiology And Cognate Medical Sciences 2009, 94: 937-946. PMID: 19429641, PMCID: PMC2742297, DOI: 10.1113/expphysiol.2009.047936.Peer-Reviewed Original ResearchConceptsAng II type 1 receptor blockerIschemic strokeEndothelin-1-induced middle cerebral artery occlusionMiddle cerebral artery occlusion modelBrain renin-angiotensin systemType 1 receptor blockerMiddle cerebral artery occlusionIpsilateral gray matterCerebral artery occlusionRenin-angiotensin systemArtery occlusion modelAnimal stroke modelsSignificant neurological impairmentCandesartan pretreatmentCerebroprotective propertiesGradual reperfusionEmbolic strokeArtery occlusionNeurological deficitsReceptor blockersSystemic pretreatmentBlood pressureCerebral ischaemiaMCAO modelInfarct size
2006
Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1–7)
Grobe JL, Mecca AP, Lingis M, Shenoy V, Bolton TA, Machado JM, Speth RC, Raizada MK, Katovich MJ. Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1–7). AJP Heart And Circulatory Physiology 2006, 292: h736-h742. PMID: 17098828, DOI: 10.1152/ajpheart.00937.2006.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAngiotensin IAngiotensin IIAnimalsBlood PressureCardiomegalyDisease Models, AnimalFibrosisHeartHypertensionMaleMyocardiumPeptide FragmentsProto-Oncogene MasProto-Oncogene ProteinsRatsRats, Sprague-DawleyReceptor, Angiotensin, Type 1Receptor, Angiotensin, Type 2Receptors, G-Protein-CoupledTime FactorsTransforming Growth Factor betaVentricular RemodelingConceptsRenin-angiotensin systemCardiac remodelingChronic infusionBlood pressureAng IIHeart failureInterstitial fibrosisAngiotensin IIMyocyte hypertrophyHyperactive renin-angiotensin systemAng II type 1Adult Sprague-Dawley ratsEffects of AngSubsequent heart failureOverexpression of angiotensinAcute myocardial infarctionMajor risk factorFormation of AngSprague-Dawley ratsCardiac tissueSubgroup of animalsChronic hypertensionAng receptorsMyocardial infarctionRisk factorsEffects of central and peripheral injections of apelin on fluid intake and cardiovascular parameters in rats
Mitra A, Katovich MJ, Mecca A, Rowland NE. Effects of central and peripheral injections of apelin on fluid intake and cardiovascular parameters in rats. Physiology & Behavior 2006, 89: 221-225. PMID: 16839572, DOI: 10.1016/j.physbeh.2006.06.006.Peer-Reviewed Original ResearchConceptsBlood pressureFluid intakeRole of apelinHypotensive actionPeripheral administrationAntidipsogenic effectPeripheral injectionSodium appetiteCardiovascular parametersSated ratsAngiotensin peptidesSprague-DawleyUnrestrained ratsApelinFluid homeostasisRatsDisparate effectsIntakeNovel peptideConsistent effectRobust effectPrevious studiesPeptidesAdministrationAppetiteChronic angiotensin-(1–7) prevents cardiac fibrosis in DOCA-salt model of hypertension
Grobe JL, Mecca AP, Mao H, Katovich MJ. Chronic angiotensin-(1–7) prevents cardiac fibrosis in DOCA-salt model of hypertension. AJP Heart And Circulatory Physiology 2006, 290: h2417-h2423. PMID: 16415071, DOI: 10.1152/ajpheart.01170.2005.Peer-Reviewed Original ResearchConceptsDOCA-salt modelBlood pressureCardiac hypertrophyCardiac fibrosisCardiac remodelingDeoxycorticosterone acetate pelletsDOCA-salt animalsBlood pressure responseCarotid artery cannulationDOCA-salt treatmentTail-cuff methodWk of treatmentPerivascular collagen depositionSprague-Dawley ratsNormal drinking waterAngiotensin fragmentsChronic angiotensinDOCA animalsAngiotensin infusionArtery cannulationPerivascular fibrosisSham surgeryAngiotensin IIOsmotic minipumpsMyocyte diameter
2005
Protection from angiotensin II‐induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats
Huentelman MJ, Grobe JL, Vazquez J, Stewart JM, Mecca AP, Katovich MJ, Ferrario CM, Raizada MK. Protection from angiotensin II‐induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats. Quarterly Journal Of Experimental Physiology And Cognate Medical Sciences 2005, 90: 783-790. PMID: 16049057, DOI: 10.1113/expphysiol.2005.031096.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAngiotensin-Converting Enzyme 2AnimalsAnimals, NewbornBlood PressureBody WeightCarboxypeptidasesCardiomyopathy, HypertrophicEndomyocardial FibrosisGene ExpressionGenetic VectorsHeartLentivirusMiceMyocardiumOrgan SizePeptidyl-Dipeptidase ARatsRats, Sprague-DawleyTransduction, GeneticConceptsRenin-angiotensin systemAngiotensin IIMyocardial fibrosisCardiac hypertrophyAngiotensin II infusionSystolic blood pressureBody weight ratioOverexpression of ACE2Potential therapeutic targetII infusionMmHg increaseBlood pressureHeart weightControl ratsDawley ratsCardiovascular diseaseEnzyme 2Protective effectTherapeutic targetMouse ACE2FibrosisHypertrophyRatsACE2Significant attenuation