Atherosclerosis is a complex inflammation condition involving the accumulation of lipid-filled macrophages within the artery wall. Progression of the initial fatty streak to an advanced atherosclerotic plaque is characterized by the development of a necrotic core region containing cholesterol and dead cells. The oxidation of low-density lipoprotein (LDL) to oxidized LDL (oxLDL) and its subsequent uptake by macrophages to form foam cells are the key process in plaque formation. OxLDL is found within atherosclerotic plaque, and it is cytotoxic to a range of cells including macrophages through the generation of reactive oxygen species (ROS) and induction of oxidative stress. The aim of this study was to examine the cytotoxic effects of oxLDL to U937 human monocyte-like cells. OxLDL caused a rapid concentration-dependent cell viability loss in U937 cells within 6 hours. The progression of oxLDL-induced cell death was found to be strongly correlated with the intracellular ROS production and intracellular glutathione (GSH) loss. OxLDL also caused a rapid loss of intracellular aconitase activity, indicating the impairment of the cellular metabolic function. The cytosolic calcium ion (Ca²⁺) level was also elevated by oxLDL, which could be from both intra- and extra-cellular sources. OxLDL also activated plasma membrane superoxide generation complex NADPH oxidase (NOX), and the progression of oxLDL-induced NOX activation was correlated with oxLDL-mediated ROS production, suggesting NOX is the major source of ROS. Further investigations using NOX inhibitors apocynin or diphenyleneiodonium (DPI) found that inhibition of NOX prevented oxLDL-induced cell viability loss, ROS production, GSH loss and aconitase activity decrease. The cytosolic Ca²⁺ elevation caused by oxLDL was also suppressed slightly by inhibiting NOX activity. These results clearly show that NOX is the major site of oxidative stress upon oxLDL activation, contributing to the oxLDL-induced cell death. This study also examined the protective effect of 7,8-dihydroneopterin (7,8-NP) on oxLDL-induced oxidative stress. 7,8-NP dramatically protected cells from oxLDL-induced cell viability loss, ROS generation and aconitase activity loss. 7,8-NP also inhibited oxLDL-induced cytosolic Ca²⁺ influx particularly after 3 hours. 7,8-NP did not inhibited mitochondrial aconitase activity decrease caused by oxLDL, nor inhibited mitochondrial ROS production. This indicates the protective effect of 7,8-NP against oxLDL damage could primarily in cytoplasm. The failure of 7,8-NP protection from oxLDL activating NOX suggests that the protection of 7,8-NP against oxLDL-induced oxidative stress was not due to the inhibition of NOX activation, but by radical scavenging activity of the NOX products.

Intracellular oxidative stress is induced by oxidised low density lipoprotein (oxLDL) in macrophages. In the atherosclerotic lesions, this oxLDL dependent oxidative stress appears to cause macrophage cell death, a key process in the development of the necrotic core within the complex plaque. Macrophages are activated by γ-interferon to synthesise and release a potent antioxidant, 7,8-dihydroneopterin (7,8-NP), which has been previously shown to protect human monocyte-like U937 cells and human monocyte-derived macrophage (HMDM) cells from oxLDL cytotoxicity. This study examined whether oxLDL causes the loss of cellular metabolic function and whether 7,8-dihydroneopterin can prevent this loss of metabolic activity in U937 cells and HMDM cells. OxLDL prepared by copper oxidation caused cell death in both U937 and HMDM cells at concentrations of 0.5 and 2.0 mg/ml, respectively. Cell morphology showed the oxLDL caused a necrotic like death in both cells as indicated by cell swelling and lysis. The decrease in cell viability was only observed after the loss of intracellular glutathione (GSH) which occurred in the first 3 hours in U937 cells following oxLDL addition. The loss of GSH appeared to be due to the production of intracellular oxidants generated in response to the presence of the oxLDL. Within 3 hours of oxLDL addition to both cell types, there was a rapid and progressive shutdown of cell metabolism indicated by a significant decrease in the enzymatic activity of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and a fall in lactate production and intracellular ATP levels. GAPDH activity was found to be inactivated rather than being lost from the cell. Gel electrophoresis with specific staining for oxidised proteins showed that the GAPDH had been oxidatively inactivated in the cells when oxLDL was present. Unlike GAPDH, lactate dehydrogenase (LDH) was not inactivated by the oxidation but was lost from the cells due to cell lysis. The observed rate of glycolysis failure was similar in both cell types except the HMDM cells did not lose lactate, LDH activity and cell viability until 6 hours compared to 3 hours with the U937 cells. The rate of oxygen consumption (VO2) was measured in U937 cells by taking cells at set time points and placing them in the respirometers to measure the VO2. U937 cells were found to increase their VO2 with incubation but this increase was inhibited in the presence of oxLDL within 3 hours. The addition of the 7,8 dihydroneopterin above 100 μM to both the U937 and HMDM cells significantly inhibited the oxLDL-induced loss of cell viability. GAPDH activity loss was also inhibited while lactate production was maintained. The 7,8-dihydroneopterin also prevented the decrease in the VO2 in oxLDL-treated U937 cells. OxLDL was labelled with fluorescent DiI to measure the uptake of oxLDL by HMDM cells. The incorporation of DiI into oxLDL was found to make it non-cytotoxic, possibly due to DiI’s antioxidant properties. Studies were therefore conducted using either a mixture of oxLDL and DiI labelled oxLDL (DiI-oxLDL) at non-protective concentrations or low concentration of DiI-oxLDL alone. These studies showed that 7,8-dihydroneopterin downregulated the oxLDL uptake in oxLDL-treated HMDM cells. Surprisingly the uptake rates also suggested that there was no relationship between oxLDL uptake and cell death assuming oxLDL and DiI-oxLDL are taken up by the same mechanism. This research showed that oxLDL-induced oxidative stress in macrophage cells causes a rapid oxidative loss of GAPDH activity which leads to the loss of glycolytic activity and a fall in ATP levels. The failure of cell metabolism appears to be a key event in the death mechanism triggered by the oxLDL. The radical scavenging activity of 7,8-dihydroneopterin appears to prevent the oxidative stress as indicated by the protection of the GSH pool. Without the oxidative stress, GAPDH remains functioning, glycolytic activity is maintained and both the U937 cells and HMDM cells did not die. This suggests that within the atherosclerotic plaque, 7,8-dihydroneopterin may act to stabilise the metabolism of macrophage cells in the presence of oxLDL and downregulate the oxLDL uptake.

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Eine der häufigsten kardiovaskulären Erkrankungen ist die Atherosklerose. Bei der Entstehung einer Atherosklerose spielt eine Hyperlipoproteinämie eine entscheidende Rolle. Ein weiterer Faktor für die Entstehung kardiovaskulärer Erkrankungen ist ein hoher Blutdruck. In dieser Arbeit wurde eine mögliche Interaktion zwischen Lipoproteinen und den blutdruckregulierenden Endothelin- und Renin-Angiotensin-Systemen untersucht. Weiterführende Analysen erfolgten an Rezeptoren für die Aufnahme von nLDL und oxLDL. Abschließend wurden Signalwege untersucht, die durch nLDL und oxLDL aktiviert werden. Tierexperimentielle Untersuchungen in Aorten und Herzen fettreich gefütterter Wildtyp- Mäuse unterstützen die Zellkultur-Ergebnisse einer Induzierung des Endothelin-Systems durch erhöhte Lipoproteine. Zusammenfassend zeigt diese Arbeit neue Mechanismen der Interaktion von Lipoproteinen und blutdruckregulierenden Systemen in Endothelzellen. Die Rezeptoren scheinen dabei eine Schlüsselrolle zu spielen. Dies spricht für eine Potenzierung von Hyperlipoproteinämie und Hypertonie bei der Entstehung von Herz-Kreislauf-Erkrankungen.

Adipositas und das polyzystische Ovarsyndrom (PCOS) sind häufig Gründe für Anovulation, Infertilität und unerfüllten Kinderwunsch. Sowohl Adipositas als auch das PCOS können zu einem Ungleichgewicht zwischen Anti- und Prooxidanzien im menschlichen Körper führen. Durch Übergewicht der Prooxidanzien ensteht oxidativer Stress. Reaktive Sauerstoffspezies (reactive oxygen species, ROS) fallen vermehrt an und oxidieren Lipoproteine zu „oxidized low density lipoproteins“ (oxLDL). Durch Bindung von oxLDL an den „lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)“ wird Apoptose und Autophagie induziert. Wir vermuten, dass sich diese Prozesse auch in der Follikelflüssigkeit (FF), dem Milieu der Eizelle, abspielen und zum Absterben reifender Follikel und somit zur Anovulation und Infertilität führen. Das Ziel dieser Arbeit war es, zu untersuchen, welchen Einfluss Adipositas, hormonelle Stimulation und PCOS auf die enzymatischen Antioxidanzien Superoxiddismutase (SOD), Katalase, Glutathionperoxidase (GPx) und Glutathionreduktase (GR) sowie auf den oxLDL-Spiegel haben. Es wurden Serum und FF von Frauen unter IVF (in vitro Fertilisation) -Therapie untersucht, die anhand ihres Body Mass Index (BMI), des Taille-Hüft-Quotienten (T/H-Quotient) sowie des PCOS in vier Gruppen eingeteilt wurden. Die Konzentration an oxLDL als Repräsentant des oxidativen Systems und die Aktivität der Enzyme SOD, Katalase, GPx und GR, Repräsentaten des antioxidativen Systems, wurden im Serum vor Stimulationsbeginn und zum Zeitpunkt der Follikelpunktion sowie in der FF gemessen. Adipöse Frauen mit und ohne PCOS hatten höhere Konzentrationen an oxLDL in der FF als normalgewichtige. Die oxLDL-Konzentrationen der FF waren 1000-fach niedriger als die der Seren. Interessanterweise waren auch die Katalase-Aktivitäten in der FF adipöser Frauen mit und ohne PCOS höher als die der normalgewichtigen. Zusammenfassend lässt sich folgern, dass erhöhte oxLDL-Konzentrationen in der FF von adipösen Frauen, unabhängig vom Vorliegen eines PCOS, mit einer gesteigerten Katalase-Aktivität und einer niedrigeren IVF-Erfolgsrate assoziiert sind.:Inhaltsverzeichnis Bibliographie III Abkürzungsverzeichnis IV 1. Einleitung 1 1.1. Infertilität 1 1.2. PCOS 2 1.2.1. Definition des PCOS 2 1.2.2. PCOS und Adipositas 3 1.3. Oxidativer Stress 4 1.3.1. Reaktive Sauerstoffspezies 4 1.3.2. Superoxiddismutase (SOD) – Schutz vor Superoxidradikalen 5 1.3.3. Katalase – Schutz vor H2O2 5 1.3.4. Glutathionperoxidase (GPx) und Glutathionreduktase (GR) 5 1.4. Oxidativer Stress, „oxidized low density lipoprotein“(oxLDL) und 6 Adipositas 1.5. Oxidativer Stress, antioxidative Enzyme und Infertilität 7 1.6. Ziele der Arbeit 9 2. Material und Methoden 10 2.1. Patientinnen und Material 10 2.2. Methoden 12 2.2.1. Follikelspektrumanalyse – Kontamination mit Blutbestandteilen 12 2.2.2. Proteinbestimmung 12 2.2.3. Bestimmung der SOD-Aktivität 13 2.2.4. Bestimmung der Katalase-Aktivität 14 2.2.5. Bestimmung der GPx-Aktivität 15 2.2.6. Bestimmung der GR-Aktivität 16 2.2.7. Bestimmung der oxLDL-Konzentration mittels ELISA 17 2.3. Statistische Auswertung 18 3. Ergebnisse 19 3.1. Vergleich der Proteinkonzentrationen in Seren und FF 19 3.2. Erhöhte SOD-Aktivität in der FF im Vergleich zum Serum 20 3.3. Erhöhte Katalase-Aktivität bei Adipositas unabhängig vom PCOS-Status 21 3.4. Erhöhte GPx-Aktivität bei adipösen Patientinnen ohne PCOS 22 3.5. Erhöhte GR-Aktivität bei Adipositas unabhängig vom PCOS-Status 23 3.6. Erhöhte oxLDL-Konzentrationen in der FF adipöser Patientinnen 25 unabhängig vom PCOS-Status 3.7. Schwangerschaftsrate der vier Patientengruppen 26 4. Diskussion 28 4.1. Das oxidative System 28 4.1.1. LOX-1 und oxLDL – Stand der Forschung 28 4.1.2. OxLDL – Diskussion der Methode 29 4.1.3. OxLDL – Konzentration im Serum 30 4.1.4. Einfluss der hormonellen Stimulationstherapie auf oxLDL 31 4.1.5. OxLDL – Konzentration in der FF 32 4.1.6. Oxidativer Status - Zusammenfassung 34 4.2. Das antioxidative System 34 4.2.1. SOD-Aktivität im Serum 35 4.2.2. SOD-Aktivität in der FF 35 4.2.2. Katalase, ein klinischer Parameter zur Bestimmung des 36 oxidativen Stress? 4.2.3. Zelltod als Ursache für erhöhte Enzymaktivitäten bei Adipositas? 36 4.2.5. Grenzen der Studie 37 4.3. Schlussfolgerung und Ausblick 38 5. Zusammenfassung 40 6. Literaturverzeichnis 44 7. Anhang 59 7.1. Tabellenverzeichnis 59 7.2. Abbildungsverzeichnis 59 7.3. Eidesstattliche Versicherung 60 7.4. Werdegang 61 7.5. Danksagung 63

Eine der häufigsten kardiovaskulären Erkrankungen ist die Atherosklerose. Bei der Entstehung einer Atherosklerose spielt eine Hyperlipoproteinämie eine entscheidende Rolle. Ein weiterer Faktor für die Entstehung kardiovaskulärer Erkrankungen ist ein hoher Blutdruck. In dieser Arbeit wurde eine mögliche Interaktion zwischen Lipoproteinen und den blutdruckregulierenden Endothelin- und Renin-Angiotensin-Systemen untersucht. Weiterführende Analysen erfolgten an Rezeptoren für die Aufnahme von nLDL und oxLDL. Abschließend wurden Signalwege untersucht, die durch nLDL und oxLDL aktiviert werden. Tierexperimentielle Untersuchungen in Aorten und Herzen fettreich gefütterter Wildtyp- Mäuse unterstützen die Zellkultur-Ergebnisse einer Induzierung des Endothelin-Systems durch erhöhte Lipoproteine. Zusammenfassend zeigt diese Arbeit neue Mechanismen der Interaktion von Lipoproteinen und blutdruckregulierenden Systemen in Endothelzellen. Die Rezeptoren scheinen dabei eine Schlüsselrolle zu spielen. Dies spricht für eine Potenzierung von Hyperlipoproteinämie und Hypertonie bei der Entstehung von Herz-Kreislauf-Erkrankungen.

Arteriosklerose mit ihren Folgeerkrankungen ist weltweit die Erkrankung mit der höchsten Mortalität und einer hohen Morbidität. Chronische Inflammationsprozesse spielen eine zentrale Rolle in der Atherogenese. Akutphaseproteinen, insbesondere dem C-reaktiven Protein (CRP) kommen als Marker chronischer Inflammationsprozesse in der Prädiktion kardiovaskulärer Ereignisse eine besondere Bedeutung zu. Erhöhte CRP-Spiegel wurden in zahlreichen Studien als Risikofaktor für Arteriosklerose und ihre Folgeerkrankungen identifiziert. Inzwischen gibt es auch einige Hinweise, die eine Rolle von CRP über die Rolle als passiver Indikator hinaus als aktiven Teilnehmer in der Arteriosklerose aufzeigen. Oxidiertes LDL ist ebenso als Risikofaktor anerkannt, die Aufnahme in Endothelzellen ist ein wichtiger Teilschritt in der Pathogenese der Arteriosklerose. Acetyliertes LDL (acLDL) wurde als Modell für oxLDL gewählt. Wir konnten nun in der FACS-Analyse zeigen dass, sich die verschiedenen Konfigurationen von CRP, monomeres CRP (mCRP) und pentameres CRP(nCRP) in der Beeinflussung der Aufnahme von acLDL in Endothelzellen unterscheiden. M-CRP führt zur Erniedrigung der Aufnahme, nCRP nicht. Dies bestätigte sich auch in der Immunfluoreszenzfärbung, die auch eine deutlichen Abnahme der acLDLAufnahme unter Einfluss von mCRP in den Endothelzellen zeigte, nCRP bewirkte dies nach 1 und 8 Stunden Inkubation nicht. Es konnte hier also gezeigt werden, dass sich die beiden CRP-Konfigurationen in der Beeinflussung des oxLDL-Metabolismus unterscheiden. Um diesen Effekt näher zu charakterisieren, untersuchten wir die Rolle der mutmaßlichen CRP-Rezeptoren auf Endothelzellen, CD16 und CD32. Sie konnten in Endothelzellen nicht nachgewiesen werden und Antikörper gegen CD16 und CD32 hatten keinen Einfluss auf die LDL-Aufnahme in Endothelzellen. Wir konnten so zeigen, dass CD16 und CD32 (mit den Isoformen a,b und c), die als Rezeptoren für mCRP und nCRP gesehen werden, nicht exprimiert wurden und so nicht an den inhibitorischen Effekten von mCRP auf die acLDLAufnahme beteiligt sind. Wir schlagen daher vor, dass andere Rezeptoren und/oder nichtrezeptorvermittelte Signalwege, wie eine Interaktion mit der Zellmembran (wie beispielsweise mit Lipid rafts), an der Entstehung des mCRP-Effektes in Endothelzellen beteiligt sind. Weitere Untersuchungen sind noch nötig, um den Effekt und seine Bedeutung in der Pathogenese der Arteriosklerose besser zu verstehen. Ansatzpunkte für zukünftige Forschungen sind beispielsweise die Signalkaskade von CRP mit seinen Konfigurationen, die Rezeptoren von CRP und die Herkunft von mCRP in vivo. / Arteriosclerosis and its associated diseases is the disease with the highest mortality worldwide and a high morbidity. Chronic Inflammation has a crucial role in Atherogenesis. Acute-phase proteins, especially C-reactive Protein (CRP) are important predictors for cardiovascular endpoints. Elevated CRP-Levels have been identified by various studies as independent risk factor for cardiovascular endpoints. There is emerging evidence for an active Role of CRP in Atherogenesis surpassing its role as a marker. Oxidized LDL (oxLDL) is well known as risk factor for arteriosclerosis, its uptake into endothelial cells is an important step in Atherogenesis. Acetylated LDL (acLDL) was chosen as model for oxLDL. We could show in FACS-Analysis, that the distinct configurations of CRP, monomeric CRP (mCRP) and pentameric CRP (nCRP) have different effects on the uptake of acLDL in endothelial cells. M-CRP decreases the uptake significantly, nCRP has no effect. This was confirmed in Immunofluorescence, where also a significant decrease in the uptake of acLDL under the influence of mCRP was seen. To further investigate this effect, we examined the role of the putative CRP-Receptors on endothelial cells, CD16 and CD32. In RT-PCR there was no mRNA expressed in the endothial cells, and function-blocking antibodies directed against CD16 and CD32 had no influence on the uptake of acLDL. We conclude, that CD16 and CD32 (with its isoforms a,b and c) are not expressed in endothelial cells and do not take part in the inhibitory effects of mCRP on the uptake of acLDL. We suggest that other receptors and/or non-receptormediated signalpathways, like an interaction with the cell membrane (e.g. lipid rafts) mediate this effect. Further investigations are needed to better understand this effect and its role in Atherogenesis, the signaling cascade of CRP and its configurations, the receptors for CRP and the origin of mCRP in vivo.

Atherosclerosis (Heart Disease) is an inflammatory disease caused by the formation of plaque within the arterial wall. In response to inflammation, monocytes enter the artery wall, differentiate into macrophages and take up altered low-density-lipoprotein (such as oxidised-LDL). This oxLDL is taken up into the phagocytotic macrophages via the action of the scavenger receptors. If more oxLDL is engulfed than the cell can process, they further differentiate into lipid-loaded foam cells. These are the main cell type found in atherosclerotic plaques. The scavenger receptor CD36 is responsible for 70% of oxLDL uptake by macrophages. Previous studies show that CD36 expression can be down regulated by the antioxidant, 7,8-dihydroneopterin. This research focuses on the effect of CD36 down regulation by 7,8-dihydroneopterin on foam cell formation. Human macrophages prepared from monocytes purified from human blood were incubated with copper oxidised LDL for up to 48 hours. Macrophage accumulation of the sterols was measured using a high performance chromatograph (HPLC) method developed as part of this project. The HPLC analysis measured: cholesterol, cholesteryl-oleate and -palmitate and 7-ketocholesterol accumulation within human macrophages. A flow cytometry procedure was developed where the strongly adherent macrophages could be lifted from the tissue culture plates before immuno staining for CD36. Effect of incubating macrophages with 7,8-dihydroneopterin on the formation of foam cells was studied by measuring the lipid content by HPLC and flow cytometry measurement of CD36. HPLC analysis showed non-cytotoxic levels of oxLDL produced a large accumulation of cholesterol and cholesteryl esters in the macrophages. Cholesterol, 7-ketocholesterol and cholesteryl-oleate and -palmitate concentrations in the cells rose significantly over the first 24 hours and stayed at a steady level for the following 24 hours. CD36 levels was further analysed on human macrophages. This study shows that foam cell formation can be measured using human macrophages. 7,8-Dihydroneopterin treatment resulted in a reduction of cholesterol and oxysterol uptake back to basal levels. It also reduced CD36 cell surface expression by a third. These results suggest that even a small reduction in CD36 cell surface expression may have a large effect on foam cell formation. This is another mechanism by which 7,8-dihydroneopterin protects against atherosclerosis developing.

Macrophage death is likely to contribute to the transformation of fatty streaks into advanced atherosclerotic lesions. Previous work in the laboratory showed that OxLDL promotes cell death in human macrophages by a mechanism involving intracellular peroxide formation. Here we show that glutathione depletion induced by OxLDL occurs independent of peroxyl radical formation. Our data suggest that the depletion of glutathione is the fundamental defect that renders macrophages susceptible to OxLDL-induced cell injury, but alone is not sufficient to kill macrophages. We indicate that increased protein-Sglutathionylation is involved in OxLDL-induced macrophage death. A potentiation of OxLDL toxicity was observed in macrophages transfected with siRNA directed against either glutathione reductase or glutaredoxin. Our data suggests that OxLDL-induced cell injury in human macrophage is mediated by the depletion of GSH, a decreased in the GSH/GSSG ratio and peroxyl radical formation. All three signals are required for OxLDL-induced macrophage death. Our results also show that the glutathione reductase/glutaredoxin system protects macrophages from OxLDL-induced cell death.

Submitted by JULIANA DE FÁTIMA PEDROSO null (dra.julianapedroso@hotmail.com) on 2018-02-07T13:11:57Z No. of bitstreams: 1 2018.pdf: 839144 bytes, checksum: 52016e060d338ad35e35f78dcd542a7e (MD5) / Approved for entry into archive by Silvana Alvarez null (silvana@ict.unesp.br) on 2018-02-07T17:16:22Z (GMT) No. of bitstreams: 1 pedroso_jf_me_sjc.pdf: 839144 bytes, checksum: 52016e060d338ad35e35f78dcd542a7e (MD5) / Made available in DSpace on 2018-02-07T17:16:22Z (GMT). No. of bitstreams: 1 pedroso_jf_me_sjc.pdf: 839144 bytes, checksum: 52016e060d338ad35e35f78dcd542a7e (MD5) Previous issue date: 2018-01-08 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A Doença Periodontal (DP) e o Diabetes Mellitus tipo 2 (DM2) apresentam a mesma etiopatogênese inflamatória e demonstram uma relação bidirecional, pois DM2 afeta a severidade da DP, e esta pode contribuir para a carga inflamatória total do indivíduo, influenciando a evolução do DM2. O objetivo do presente estudo foi avaliar os fatores de risco para o desenvolvimento de aterosclerose em pacientes portadores de DM2, com e sem periodontite crônica. Foram analisados 48 pacientes, os quais foram divididos em 2 grupos: Teste (pacientes diabéticos com periodontite crônica) e Controle (pacientes diabéticos sem periodontite crônica). O grupo teste foi tratado com debridamento periodontal e o grupo controle recebeu profilaxia supragengival. Ambos os grupos receberam controle de placa a cada 3 meses. No baseline e 6 meses após o tratamento, foi realizada tomada dos parâmetros clínicos periodontais (IP, IG, PS, RG e NIC) e coleta de sangue para avaliação dos marcadores séricos inflamatórios (oxLDL, CT, TG, LDL, HDL, glicose, HbA1c, PCRus, leucócitos e neutrófilos). Os parâmetros periodontais mostraram melhora significativa (p<0,05) no grupo teste, exceto RG. IP e IG também diminuíram significativamente no grupo controle após 6 meses. CT e HbA1c apresentaram taxas significativamente maiores no grupo teste, em comparação com o grupo controle. As taxas de PCR-us e HbA1c diminuíram significativamente no grupo teste após a terapia periodontal. A contagem de leucócitos mostrou uma diminuição relevante no grupo controle durante o tempo do estudo. A terapia periodontal promove melhoras nos parâmetros clínicos periodontais, nos parâmetros inflamatórios e nas taxas de HbA1c em pacientes portadores de DM2 e periodontite, mas não interfere nos níveis séricos de oxLDL. / Periodontal Disease (DP) and Type 2 Diabetes Mellitus (DM2) present the same inflammatory etiopathogenesis and demonstrate a bidirectional relationship, since DM2 affects the severity of PD, and this may contribute to the individual's total inflammatory load, influencing the evolution of DM2. The objective of the present study was to evaluate the risk factors for the development of atherosclerosis in patients with T2DM, with and without chronic periodontitis. We analyzed 48 patients, who were divided into 2 groups: Test (diabetic patients with chronic periodontitis) and Control (diabetic patients without chronic periodontitis). The test group was treated with periodontal debridement and the control group received supragingival prophylaxis. Both groups received plaque control every 3 months. Periodontal clinical parameters (IP, IG, PS, RG and NIC) and collection of blood for evaluation of serum inflammatory markers (oxLDL, CT, TG, LDL, HDL, glucose, HbA1c, hs-CRP, leukocytes and neutrophils). The periodontal parameters showed significant improvement (p <0.05) in the test group, except for RG. IP and IG also decreased significantly in the control group after 6 months. CT and HbA1c presented significantly higher rates in the test group compared to the control group. Rates of Hs-1c and HbA1c decreased significantly in the test group after periodontal therapy. The leukocyte count showed a significant decrease in the control group during the study time. Periodontal therapy promotes improvements in periodontal clinical parameters, inflammatory parameters and HbA1c rates in patients with DM2 and periodontitis, but does not interfere with serum levels of oxLDL.