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Vascular and cardiac alteration in different pathologies: obesity, diabetes, acute and chronic sepsis, Zica and Dengue infection, and others situations.
Federal University of Minas Gerais (UFMG)
English; Italian; Spanish
Type of Research Project
- Basic science
What is the background of the project?
Vascular endothelium is a crucial regulator of vascular function and homeostasis. Many inflammatory or infectious diseases lead to changes in cardiac and/or vascular function, increasing the probability of occurrence of cardiovascular diseases. For example, sepsis-surviving patients have a high risk of developing cardiovascular diseases. Besides, biologically active tissue, such as perivascular adipose tissue (PVAT), release both vasoconstrictor and vasodilators factors. The literature shows that the anti-contractile effect induced by PVAT may be due to activation of the renin-angiotensin system (RAS). Knowing that the leading cause of death in the world is due to cardiovascular diseases (31%), a better understanding of how they can be triggered may favor the existence of a prophylactic treatment that reduces their incidence.
What is the aim of the project?
Our objective is to investigate how systemic inflammatory and/or infection processes cause changes in cardiovascular functions and therefore how we can intervene on those process in a way to breakthrough with a prophylactic treatment.
What techniques and methods are used?
Different animal models are used mimicking the inflammatory or infectious process to be studied. For vascular function study we perform experiments of vascular reactivity in the presence of antagonists, inhibitors or blockers of the pathways to be investigated through endothelial integrity. Endothelial integrity may be assessed qualitatively by the degree of relaxation induced by acetylcholine in the presence of contractile tone induced by phenylephrine. Endothelial samples are obtained on animal models aorta. For cardiac function are used Langhendorff methods, cardiac electrophysiology and electrocardiogram. In the Langendorff preparation, the heart is removed from the animal's body, severing the blood vessels; it is then perfused in a reverse fashion via the aorta, usually with a nutrient rich, oxygenated solution. Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording – a graph of voltage versus time – of the electrical activity of the heart using electrodes placed on the skin. In addition, studies such as gene and protein expression quantification we performed. We use polymerase chain reaction (PCR) technique to amplify the genes and then we use bacteria to express the specific proteins. PCR is a method widely used in molecular biology to make several copies of a specific DNA segment. Using PCR, copies of DNA sequences are exponentially amplified to generate thousands to millions of more copies of that particular DNA segment. Possible inflammatory mediators or vascular/cardiac tonus are measured by immunoassay enzyme, fluorescence microscopy or confocal. We usually use Enzyme-Linked Immunosorbent Assay as the main immunoassay. Performing an ELISA involves at least one antibody with specificity for a particular antigen. The sample with an unknown amount of antigen is immobilized on a solid support (usually a polystyrene microtiter plate) either non-specifically (via adsorption to the surface) or specifically (via capture by another antibody specific to the same antigen, in a "sandwich" ELISA). After the antigen is immobilized, the detection antibody is added, forming a complex with the antigen. The detection antibody can be covalently linked to an enzyme or can itself be detected by a secondary antibody that is linked to an enzyme through bioconjugation. Between each step, the plate is typically washed with a mild detergent solution to remove any proteins or antibodies that are non-specifically bound. After the final wash step, the plate is developed by adding an enzymatic substrate to produce a visible signal, which indicates the quantity of antigen in the sample. Using all the techniques described above we can investigate how systemic inflammatory and/or infection processes cause changes in cardiovascular functions.
What is the role of the student?
- The student will mainly observe
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
To learn the techniques in the field of cardiovascular science and to help undergraduated students in their experiments, such as manipulation of samples and learning how to use many useful laboratory equipment. We require the student to study the recommended articles. Besides, we expect the undergraduated student to present by the end of his research internship his experiences, outcomes and possible suggestions to improve the program.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes, theoretical teaching will be provided for the student by the tutor as well as by other laboratory researchers. The theorical topics to be addressed include cardiovascular and renal physiology, specifically renin angiotensin system. This theorical teaching will be conducted with papers related to the topic as well as with the weekly lab meeting.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
The student needs to have knowledge of cardiovascular and renal physiology, as well as biochemistry. If the student has pharmacological knowledge it would be better. Subjects passed: biochemistry, physiology.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system - Students in biomedical fields
- Nóbrega N; Araújo NF; Reis D; Facine LM; Miranda CAS; Mota GC; et al. Hydrogen peroxide and nitric oxide induce anticontractile effect of perivascular adipose tissue via renin angiotensin system activation. Nitric Oxide. 2019 Mar 1;84:50-59. doi: 10.1016/j.niox.2018.12.011. Epub 2019 Jan 3.
- Diniz MC; Olivon VC; Tavares LD; Simplicio JA; Gonzaga NA; de Souza DG; et al. Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase-derived prostanoids. Life Sci. 2017 May 1;176:26-34. doi: 10.1016/j.lfs.2017.03.016. Epub 2017 Mar 21.
- Kangussu LM; Olivon VC; Arifa RD; Araújo N; Reis D; Assis MT. Enhancement on reactive oxygen species and COX-1 mRNA levels modulate the vascular relaxation induced by sodium nitroprusside in denuded mice aorta. Fundam Clin Pharmacol. 2015 Apr;29(2):150-63. doi: 10.1111/fcp.12103. Epub 2015 Feb 27.
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