AimsHSPA12B is a newly discovered and endothelial-cell-specifically expressed heat shock protein. We have reported recently that overexpression of HSPA12B increased endothelial nitric oxide synthase (eNOS) expression in mouse cardiac tissues during endotoxemia. Endothelial NOS has been shown to protect heart from ischaemic injury. We hypothesized that overexpression of HSPA12B will attenuate cardiac dysfunction and remodelling after myocardial infarction (MI) through an eNOS-dependant mechanism.Methods and resultsMI was induced by permanent ligation of the left anterior descending coronary artery in the transgenic mice (Tg) overexpressing hspa12b gene and its wild-type (WT) littermates. Echocardiographic analysis revealed that Tg mice exhibited improvements in cardiac dysfunction and remodelling at 1 and 4 weeks after MI. These improvements were accompanied by a significant decrease in cardiomyocyte apoptosis and increase in capillary and arteriolar densities. Significant up-regulation of eNOS, VEGF, Ang-1, and Bcl-2 was also observed in Tg hearts compared with WT hearts after MI. However, pharmacological inhibition of eNOS abolished the HSPA12B-induced decrease in cardiomyocyte apoptosis and increase in capillary formation after MI. Most importantly, inhibition of eNOS abrogated the protection of HSPA12B against cardiac dysfunction and remodelling after MI.ConclusionsThese data demonstrate for the first time that the overexpression of HSPA12B attenuates cardiac dysfunction and remodelling after MI. This action of HSPA12B was mediated, at least in part, by prevention of cardiomyocyte apoptosis and promotion of myocardial angiogenesis via an eNOS-dependent mechanism. HSPA12B could be a novel target for the management of patients with post-MI cardiac dysfunction and remodelling.

No description available.

No description available.

Purpose: Translational research characterizing endothelial dysfunction and the progression of cardiovascular disease (CVD) is necessary for understanding the complex nature of multi-factorial diseases. Perhaps more important though, is understanding the compensatory and adaptive processes associated with regression of diseases and chronic oxidative stress. Vascular endothelial growth factor (VEGF) is an important protein in endothelial health and nitric oxide (NO) production. The purpose of this research was to examine changes in VEGF-mediated endothelial nitric oxide synthase (eNOS) activity under conditions of oxidative stress both in vivo and in vitro. Methods: The oxidative stress relationship involving plasma VEGF, NO, and hydrogen peroxide (H2O2) was assessed in sedentary, pre-hypertensive African American participants both (n=48) before and following (n=22) 6 months of aerobic exercise training (AEXT). In vitro, H2O2 exposure along with atherogenic, 4 dyne/cm2, and athero-protective, 20 dyne/cm2, levels of laminar shear stress (LSS) were used to characterize VEGF-mediated eNOS activity to gain insights into physiological signaling. Results: At baseline, VEGF levels increased with increasing blood pressure (BP) level while NO levels decreased from normotensive to hypertensive participants. H2O2 levels also trended upward with increasing BP level, and in vitro H2O2 was observed to decrease VEGF-mediated eNOS activity in a dose dependent manner. Following AEXT, participants were divided into groups relative to their BP change following the intervention. Participants that decreased their BP level demonstrated a decrease in VEGF and H2O2 level. In addition, following 24 hrs of LSS at 20 dyne/cm2, VEGF-mediated eNOS activity and VEGFR2 protein expression was significantly lower compared to 24 hrs of LSS at 4 dyne/cm2. Discussion: Increased circulating levels of VEGF in vivo may be a compensatory mechanism. Endothelial dysfunction and progressive CVD may trigger such compensation. The adaptive response to exercise for its BP-lowering effects is systemic and encompasses many changes. These beneficial adaptations have likely alleviated the compensatory mechanism of elevated VEGF levels seen at baseline. Indeed, following 24 hrs of an athero-protective LSS level, VEGF-mediated eNOS activity was significantly lower compared to 24 hr of LSS at an atherogenic level. The difference in VEGF-mediated eNOS activity may be due, in part, to the decrease in VEGFR2 protein expression we observed under an athero-protective LSS level. / Kinesiology

L’angiogenèse est la formation de nouveaux vaisseaux sanguins à partir d’un réseau vasculaire existant. C’est un phénomène essentiel pour des processus physiologiques et pathologiques. L’activation des cellules endothéliales est contrôlée par plusieurs facteurs de croissance. Le VEGF et son récepteur le VEGFR-2 ont été prouvés comme étant spécifiques et critiques pour la formation des vaisseaux sanguins alors que Tie2, le récepteur auquel se lie l’Ang-1, est requis aussi bien dans le développement vasculaire que dans l’angiogenèse tumorale. Il est connu que l’activation de Tie2 est nécessaire à la stabilisation finale de la vascularisation en inhibant la perméabilité vasculaire induite par le VEGFR-2. Nous avons premièrement découvert que le facteur de croissance pro-angiogénique, l’Ang-1 contrecarre les effets de perméabilité cellulaire induits par le VEGF en inhibant la production de NO dans les cellules endothéliales. Cet effet inhibiteur de Tie2 intervient directement au niveau de l’activité de l’enzyme eNOS. Suite à l’activation de Tie2 par l’Ang-1, eNOS devient fortement phosphorylé sur la Thr497 après la phosphorylation et l’activation de la PKCζ. Nos résultats suggèrent que l’inhibition, par Tie2, de la perméabilité vasculaire durant l’angiogenèse serait due, en partie, à l’inhibition de la production de NO. Deuxièmement nous avons pu distinguer entre deux modes de migration cellulaire endothéliale induits par l’Ang-1 et le VEGF. À l’opposé du VEGF qui promeut une migration individuelle aléatoire, l’Ang-1 induit une migration collective directionnelle. Dans cette étude, nous avons identifié la β-caténine comme un nouveau partenaire moléculaire de la PKCζ. Cette association de la PKCζ à la β-caténine amène le complexe de polarité Par6-aPKC et le complexe des jonctions d’adhérences cellulaires à interagir ensemble à deux localisations différentes au niveau de la cellule endothéliale. Au niveau des contacts intercellulaires, le complexe PKCζ/β-caténine maintien la cohésion et l’adhésion cellulaire nécessaire pour le processus migratoire collectif. Ce complexe se retrouve aussi au niveau du front migratoire des cellules endothéliales afin d’assurer la directionalité et la persistance de la migration endothéliale en réponse à l’Ang-1. D’une manière intéressante, lors de l’inhibition de la PKCζ ou de la β-caténine on assiste à un changement du mode de migration en réponse à l’Ang-1 qui passe d’une migration directionnelle collective à une migration individuelle aléatoire. Ce dernier mode de migration est similaire à celui observé chez des cellules endothéliales exposées au VEGF. Ces résultats ont été corroborés in vivo par une polarité et une adhésion défectueuses au cours de la vasculogenèse chez le poisson zèbre déficient en PKCζ. En résumé, Ang-1/Tie2 module la signalisation et les réponses biologiques endothéliales déclenchées par le VEGF/VEGFR-2. L’identification des mécanismes moléculaires en aval de ces deux récepteurs, Tie2 et VEGFR-2, et la compréhension des différentes voies de signalisation activées par ces complexes moléculaires nous permettra de mettre la lumière sur des nouvelles cibles thérapeutiques pour le traitement des maladies angiogéniques. / Angiogenesis is the formation of new blood vessels from a pre-existing vascular network. It is an essential mechanism for many physiological and pathological conditions. Also, the general mechanism in both conditions remains the same. VEGF and its receptor VEGFR-2 have been proven to be specific and critical for blood vessel formation. The Angiopoietin-1 receptor, Tie2, is required for vascular development as well as in tumor angiogenesis. It is known that the activation of Tie2 is required for vascular stabilization by inhibiting vascular permeability induced by VEGFR-2. First, we found that the pro-angiogenic growth factor, Ang-1 counteracts the effects of VEGF-induced permeability by inhibiting NO production by endothelial cells. This inhibitory effect of Tie2 acts directly on eNOS activity. Following activation of Tie2 by Ang-1, eNOS becomes highly phosphorylated on the inhibitory site, the Thr497, following PKCζ phosphorylation and activation. Our results suggest that the inhibition by Tie2 of vascular permeability during angiogenesis is due, in part, to the inhibition of NO production. In our second study we distinguished between two types of endothelial cell migration induced by Ang-1 and VEGF. At the opposite of Ang-1 that induced collective and directional cell migration, VEGF promoted individual and random cell motility. We identified β-catenin as a new molecular partner of PKCζ. This association of PKCζ with β-catenin brings the Par6-aPKC polarity complex and the adherens junctions complex to interact with each other at two different locations in endothelial cells. PKCζ/β-catenin complex is located specifically at cell-cell contacts to maintain cohesion and cell adhesion necessary for the collective migration process. This complex was located also at the leading edge of endothelial cells during migration to ensure the directionality and the persistence of migration in response to Ang-1. In addition, inhibition of PKCζ or β-catenin switched the migration mode, in response to Ang-1, from directional and collective to a more random and individual cell migration which resembles the type of migration of endothelial cells exposed to VEGF. These results were confirmed in vivo by aberrant cell polarity and cell adhesion defects of tip cell during vascular sprouting of intersegmental vessels in PKCζ deficient zebrafish embryos. In summary, Ang-1/Tie2 modulates endothelial cell signaling and biological responses induced by VEGF/VEGFR-2. The identification of molecular mechanisms involved in the action of these two receptors, VEGFR-2 and Tie2, and the understanding of the different signaling pathways activated by these molecular complexes will allow us to identify new therapeutic targets for the treatment of angiogenic diseases treatment.

L’angiogenèse est la formation de nouveaux vaisseaux sanguins à partir d’un réseau vasculaire existant. C’est un phénomène essentiel pour des processus physiologiques et pathologiques. L’activation des cellules endothéliales est contrôlée par plusieurs facteurs de croissance. Le VEGF et son récepteur le VEGFR-2 ont été prouvés comme étant spécifiques et critiques pour la formation des vaisseaux sanguins alors que Tie2, le récepteur auquel se lie l’Ang-1, est requis aussi bien dans le développement vasculaire que dans l’angiogenèse tumorale. Il est connu que l’activation de Tie2 est nécessaire à la stabilisation finale de la vascularisation en inhibant la perméabilité vasculaire induite par le VEGFR-2. Nous avons premièrement découvert que le facteur de croissance pro-angiogénique, l’Ang-1 contrecarre les effets de perméabilité cellulaire induits par le VEGF en inhibant la production de NO dans les cellules endothéliales. Cet effet inhibiteur de Tie2 intervient directement au niveau de l’activité de l’enzyme eNOS. Suite à l’activation de Tie2 par l’Ang-1, eNOS devient fortement phosphorylé sur la Thr497 après la phosphorylation et l’activation de la PKCζ. Nos résultats suggèrent que l’inhibition, par Tie2, de la perméabilité vasculaire durant l’angiogenèse serait due, en partie, à l’inhibition de la production de NO. Deuxièmement nous avons pu distinguer entre deux modes de migration cellulaire endothéliale induits par l’Ang-1 et le VEGF. À l’opposé du VEGF qui promeut une migration individuelle aléatoire, l’Ang-1 induit une migration collective directionnelle. Dans cette étude, nous avons identifié la β-caténine comme un nouveau partenaire moléculaire de la PKCζ. Cette association de la PKCζ à la β-caténine amène le complexe de polarité Par6-aPKC et le complexe des jonctions d’adhérences cellulaires à interagir ensemble à deux localisations différentes au niveau de la cellule endothéliale. Au niveau des contacts intercellulaires, le complexe PKCζ/β-caténine maintien la cohésion et l’adhésion cellulaire nécessaire pour le processus migratoire collectif. Ce complexe se retrouve aussi au niveau du front migratoire des cellules endothéliales afin d’assurer la directionalité et la persistance de la migration endothéliale en réponse à l’Ang-1. D’une manière intéressante, lors de l’inhibition de la PKCζ ou de la β-caténine on assiste à un changement du mode de migration en réponse à l’Ang-1 qui passe d’une migration directionnelle collective à une migration individuelle aléatoire. Ce dernier mode de migration est similaire à celui observé chez des cellules endothéliales exposées au VEGF. Ces résultats ont été corroborés in vivo par une polarité et une adhésion défectueuses au cours de la vasculogenèse chez le poisson zèbre déficient en PKCζ. En résumé, Ang-1/Tie2 module la signalisation et les réponses biologiques endothéliales déclenchées par le VEGF/VEGFR-2. L’identification des mécanismes moléculaires en aval de ces deux récepteurs, Tie2 et VEGFR-2, et la compréhension des différentes voies de signalisation activées par ces complexes moléculaires nous permettra de mettre la lumière sur des nouvelles cibles thérapeutiques pour le traitement des maladies angiogéniques. / Angiogenesis is the formation of new blood vessels from a pre-existing vascular network. It is an essential mechanism for many physiological and pathological conditions. Also, the general mechanism in both conditions remains the same. VEGF and its receptor VEGFR-2 have been proven to be specific and critical for blood vessel formation. The Angiopoietin-1 receptor, Tie2, is required for vascular development as well as in tumor angiogenesis. It is known that the activation of Tie2 is required for vascular stabilization by inhibiting vascular permeability induced by VEGFR-2. First, we found that the pro-angiogenic growth factor, Ang-1 counteracts the effects of VEGF-induced permeability by inhibiting NO production by endothelial cells. This inhibitory effect of Tie2 acts directly on eNOS activity. Following activation of Tie2 by Ang-1, eNOS becomes highly phosphorylated on the inhibitory site, the Thr497, following PKCζ phosphorylation and activation. Our results suggest that the inhibition by Tie2 of vascular permeability during angiogenesis is due, in part, to the inhibition of NO production. In our second study we distinguished between two types of endothelial cell migration induced by Ang-1 and VEGF. At the opposite of Ang-1 that induced collective and directional cell migration, VEGF promoted individual and random cell motility. We identified β-catenin as a new molecular partner of PKCζ. This association of PKCζ with β-catenin brings the Par6-aPKC polarity complex and the adherens junctions complex to interact with each other at two different locations in endothelial cells. PKCζ/β-catenin complex is located specifically at cell-cell contacts to maintain cohesion and cell adhesion necessary for the collective migration process. This complex was located also at the leading edge of endothelial cells during migration to ensure the directionality and the persistence of migration in response to Ang-1. In addition, inhibition of PKCζ or β-catenin switched the migration mode, in response to Ang-1, from directional and collective to a more random and individual cell migration which resembles the type of migration of endothelial cells exposed to VEGF. These results were confirmed in vivo by aberrant cell polarity and cell adhesion defects of tip cell during vascular sprouting of intersegmental vessels in PKCζ deficient zebrafish embryos. In summary, Ang-1/Tie2 modulates endothelial cell signaling and biological responses induced by VEGF/VEGFR-2. The identification of molecular mechanisms involved in the action of these two receptors, VEGFR-2 and Tie2, and the understanding of the different signaling pathways activated by these molecular complexes will allow us to identify new therapeutic targets for the treatment of angiogenic diseases treatment.

ARF6 et ARF1 sont des petites GTPases de la famille des ARF(s) qui régulent plusieurs voies de signalisation comprenant, la formation et le mouvement des vésicules, la transformation des lipides membranaires et la réorganisation du cytosquelette d’actine. À ce jour, le rôle de la protéine ARF6 et de la protéine ARF1 dans la signalisation des récepteurs couplés aux protéines G (RCPG) et des récepteurs à activité tyrosine kinase (RTK) dans les cellules endothéliales est encore très peu étudié. Le but de cette étude a été de caractériser le rôle de la protéine ARF6 dans la migration des cellules endothéliales induite par l’endothéline-1, ainsi que le rôle de la protéine ARF1 dans la sécrétion du monoxyde d’azote (NO) stimulées par le VEGF. Dans cette étude, nous montrons qu’ARF6 est essentielle à la migration des cellules endothéliales induite par l’endotheline-1. L’inhibition de l’expression d’ARF6 par interférence à l’ARN entraîne une activation marquée de la kinase FAK et son association constitutive avec Src. Par ailleurs, cette inhibition affecte l’association entre GIT1 et la kinase FAK. Ceci se traduit par une inhibition du désassemblage des contacts focaux et une augmentation de l’adhésion cellulaire menant à une diminution de la motilité. De plus, nos résultats montrent que la protéine ARF1 est essentielle à l’activation d’eNOS et à la sécrétion du NO suite à l’activation du VEGFR2 dans les cellules endothéliales BAEC. En effet, l’inhibition de l’expression d’ARF1 par interférence à l’ARN entraîne une inhibition du recrutement de la kinase Akt à la membrane plasmique et une inhibition de son activation induite par le VEGF. L’inhibition de l’activation de la kinase Akt par le VEGF conduit à une inhibition de l’activation de eNOS et de la sécrétion du NO. Dans l’ensemble, nos résultats montrent que les protéines ARF6 et ARF1 sont essentielles à la signalisation de l’ETB et du VEGFR2 pour les processus menant à la migration cellulaire et à la sécrétion du NO respectivement, deux évènements essentiels à l’angiogenèse. / ARF6 and ARF1 are small GTPases of the ARF family(s) that regulate several signalling pathways including vesicles trafficking, lipid membrane remodelling and actin cytoskeleton reorganization. To date, the role of ARF6 and ARF1 in GPCR and RTK signalling, in endothelial cells, is little known. In this thesis, we aimed to characterize the role of ARF6 in the migration of endothelial cells induced by Enodothelin-1, and the role of ARF1 in the secretion of NO induced by VEGF. We show that ARF6 is essential for endothelial cell migration induced by endothelin-1. Inhibition of ARF6 expression using RNA interference markedly impaired basal and ET-1 stimulated cell migration. In this condition, FAK is found constitutively associated with Src. In contrast, depletion of ARF6 impairs the ability of GIT1 to form an agonist-promoted complex with FAK, thereby preventing disassembly of focal adhesions. As a consequence, adhesion of ARF6-depleted endothelial cells is increased and their motility is reduced. Furthermore, our result shows that ARF1 GTPase is essential for the activation of eNOS and the secretion of NO following VEGFR2 activation in endothelial cells. Inhibition of ARF1 expression using RNA interference markedly impaired the recruitment of Akt to the plasma membrane and its phosphorylation by the VEGF. As a consequence, the inhibition of Akt leads to an inhibition of eNOS, a well known downstream target, which in turn leads to inhibition of NO production. All together, our results indicate that ARF6 and ARF1 are essential for the ETB and the VEGFR2 signalling leading to cell migration and NO secretion respectively, two required steps for angiogenesis.

Traumatic brain injury (TBI) is the most frequent cause of death in children and young adults in the United States. Besides emergency neurosurgical procedures, there are few medical treatment options to improve recovery in people who have experienced a TBI. Management of patients who survive TBI is complicated by both central nervous system and peripheral systemic effects. The pathophysiology of systemic inflammation and coagulopathy following TBI has been attributed to trauma-induced endothelial cell dysfunction; however, there is little knowledge of the mechanisms by which trauma might impact the functions of the vascular endothelium at sites remote from the injury. The endothelium lining these small vessels normally produces nitric oxide (NO), arachidonic acid metabolites, and endothelial-dependent hyperpolarizing factors to relax the surrounding vascular smooth muscle. For this research study we investigated the effects of fluid-percussion-induced TBI on endothelial-dependent vasodilatory functions in a remote tissue bed (the mesenteric circulation) 24 hours after injury. We hypothesized that TBI causes changes in the mesenteric artery endothelium that result in a loss of endothelial-dependent vasodilation. We found that vasodilations induced by the muscarinic-receptor agonist, acetylcholine, are attenuated following TBI. While the endothelial-derived hyperpolarizing component of vasodilation was preserved, the NO component was severely impaired. Therefore, we tested whether the loss of NO component was due to a decrease in bioavailablity of the NO synthase (NOS) cofactor BH4, the NOS substrate L-arginine, or to changes in expression/activity of the enzyme arginase, which competes with NOS for L-arginine. We found that supplementation of L-arginine and inhibition of the enzyme arginase rescues endothelial-dependent vasodilations in TBI arteries. This study demonstrates that there are pathological systemic effects outside the point of injury following TBI leading to a dysfunctional endothelial vasodilatory pathway. These data provide insight into the pathophysiology of endothelial dysfunction after trauma and may lead to new potential targets for drug therapy.

Dentre as espécies florestais, o Eucalyptus é o gênero florestal mais plantado no Brasil, com aproximadamente 7,8 milhões de hectares, tendo grande importância econômica para o país. Desta maneira, é importante um melhor conhecimento e quantificação dos fatores que condicionam e reduzem o crescimento e a produtividade das florestas. Assim, este estudo teve por objetivos: i) adaptar, calibrar e avaliar o Modelo da Zona Agroecológica (MZA-FAO) para a estimação do crescimento e da produtividade de oito clones de eucalipto em diferentes regiões brasileiras; ii) determinar a magnitude e as principais causas das quebras de produtividade (yield gaps) da cultura do eucalipto em diferentes regiões produtoras do estado de Minas Gerais; e iii) avaliar a influência de eventos de El Niño, La Niña e Neutros na produtividade de eucaliptos em diferentes localidades produtoras do Brasil. Foram adaptados e calibrados os coeficientes do MZA-FAO, como a correção para o índice de colheita (Cc), o coeficiente de sensibilidade ao déficit hídrico (ky), as curvas características de índice de área foliar (IAF), crescimento radicular (Zr) e coeficiente de cultura (kc), além da inclusão de funções de penalização da produtividade do eucalipto por ocorrência de eventos de geada (ffrost) e mortalidade por longos períodos de deficiência hídrica (fwd). A inclusão das funções de penalização e a calibração dos coeficientes resultaram em uma melhora significativa no desempenho (acurácia e precisão) do modelo, com a REQM passando de 110 m3 ha-1, na fase inicial de calibração, para 39 m3 ha-1, na fase final de calibração, R2 passando de 0,73 para 0,82 e índice d indo de 0,70 para 0,93. Com relação às quebras de produtividade, a deficiência hídrica foi o principal fator de quebra de produtividade, correspondendo a 77% da quebra total (QT), enquanto que as perdas decorrentes do déficit de manejo corresponderam a 23% da QT. Para avaliar o crescimento do eucalipto em eventos de ENOS, no período de 1983 a 2016, foi considerado o Incremento Corrente Anual (ICA) no período de máximo crescimento, ou seja, no 3° ano de seu ciclo. As produtividades e as perdas de produtividade do eucalipto durante a atuação dos eventos de ENOS mostraram-se amplamente variáveis tanto espacialmente quanto temporalmente, como consequência dos diferentes regimes térmicos e hídricos das regiões produtoras, não sendo observado um padrão claro para a relação ENOS e produtividade do eucalipto em diferentes regiões brasileiras avaliadas. / Among the forest species, the Eucalyptus is the most planted one in Brazil, with approximately 7.8 million hectares, having a huge economic importance for the country. Therefore, a better knowledge and quantification of the factors that affect forests growth and yield is of high important. Based on that, this study had as objectives: i) to adapt, calibrate and evaluate the Agroecological Zone Model (AEZ-FAO) to estimate growth and yield of eight eucalyptus clones in different Brazilian producing regions; ii) to identify the magnitude and major causes of yield gaps of eucalyptus in different producing regions of Minas Gerais state, Brazil; and iii) to identify the influence of El Niño, La Niña and Neutral events on eucalyptus yield in 12 Brazilian producing regions. The model´s coefficients, such as correction for the harvest index (Cc), water deficit sensitivity index (ky), leaf area index curve (LAI), root growth curve (Zr) and crop coefficient (kc), were calibrated. Penalization functions for considering the occurrence of frost events (ffrost) and mortality by long periods of accumulated water deficit (fwd) were also included in the model. The calibration and adaptation of the model resulted in a significant improvement of its performance (accuracy and precision), for both calibration and evaluation phases. The RMSE was 110 m3 ha-1 in the initial phase of calibration while in the final phase, RMSE was reduced to 39 m3 ha-1, the R2 was increase from 0.73 to 0.82, and the agreement index (d) was also improved going from 0.70 to 0.93. In relation to the yield gaps, the water deficit was the main factor of yield reduction, corresponding to 77% of the total yield gap (YGT), while losses due to sub-optimum management corresponded to 23% of YGT. In order to evaluate the eucalyptus growth under different ENSO events, from 1983 to 2016, the Current Annual Increment (CAI) in the period of maximum growth, 3rd year of the cycle, was used. The eucalyptus yield and yield gap during the ENSO events were widely variable both spatially and temporally as a consequence of the different thermal and water regimes of the producing regions. It was not possible to identify a clear pattern thee relationship between ENSO and eucalyptus yield in the different Brazilian regions assessed.

A importância do Estado de São Paulo (ESP) é notável no desenvolvimento do Brasil, seja no setor econômico ou energético, o que justifica o estudo do comportamento do clima nessa região. O conhecimento da variabilidade da precipitação é imprescindível na gestão de recursos hídricos e possui grande impacto na agricultura e geração de energia por meio de fontes hidrelétricas. Estudos anteriores apontaram efeitos não-lineares do El Niño-Oscilação Sul (ENOS) sobre a precipitação no ESP; entretanto, nenhum estudo específico acerca da influência da Oscilação interdecadal do Pacífico (ODP) nesta área foi ainda realizado, embora haja alguns impactos conhecidos na América do Sul. Deste modo, este trabalho estudou a relação entre anomalias de precipitação no ESP e a ODP, no período de 1901 a 2007, de forma a auxiliar as pesquisas na linha da previsão climática nessa região do Brasil. Na primeira etapa, foram descritos os regimes de precipitação tanto para a América do Sul como localmente, para o ESP, onde se destacaram fatores como a topografia e a influência do Oceano Atlântico. Posteriormente, foram calculados quantis anuais e mensais que permitiram classificar cada evento quanto ao total de precipitação. Regiões pluviometricamente homogêneas foram determinadas no ESP com base na climatologia e nos quantis de precipitação. Notou-se a relação construtiva entre eventos ENOS e as fases da ODP, com máximo durante o verão austral. Os sinais da ODP são percebidos em todo o ESP principalmente na primavera e no verão austrais. Uma análise complementar mostrou que as fases da Oscilação Multidecadal do Atlântico (AMO) também contribuem para a precipitação no ESP durante o verão e a primavera austrais no litoral, durante o verão no interior, e ao longo da primavera na região da Serra da Mantiqueira. Aparentemente, não há relação entre os eventos ENOS e a AMO. / São Paulo State (SPS) is remarkably important to the development of Brazil, economically or energetically, and this justifies climate studies on that region. Knowing rainfall variability is essential to water resources management and it has a great impact on agriculture an power production by hydroelectric power plants. Previous studies have detected non-linear effects of El Niño-Southern Oscillation (ENSO) on SPS rainfall however no specific work deals with PDO influence in this area besides some impacts on South America are known. Therefore this work has studied the relationship between rainfall anomalies in SPS and PDO from 1901 to 2007 to contribute to the climate forecasting improvement. First it was described the rainfall regime in South America, and locally in SPS where topography and the Atlantic Ocean influences were of special importance. Then annual and monthly quantiles were calculated to allow the classification of events according to rainfall totals. Rainfall homogeneous regions were established in SPS using climatology and quantiles. It was observed the constructive relationship between ENSO events and PDO phases, mainly on austral summer. PDO signals were noticed all over the SPS mostly on austral spring and summer. An additional analysis showed that Atlantic Multidecadal Oscillation (AMO) phases also contribute to SPS rainfall during austral summer and spring at the coast, only on summer at the country and during spring at the Mantiqueira Slopes. Apparently, there is no relation between ENSO events and AMO phases.