Discipline: Biological Sciences
Subcategory: Physiology and Health
Maurice A. Whalen, Jr. - Tougaloo College
Co-Author(s): Elizabeth Harrington, Brown University, RI
The atrial natriuretic peptide (ANP) enhances endothelium barrier dysfunction, normalizes endothelium permeability, and attenuates pulmonary edema through natriuretic peptide receptor-C (NPR-C). Significance: To this day, acute lung injury (ALI) accounts for a majority of morbidity and mortality cases within terminally ill patient population. Though many definitions have been given, ALI will be define as an acute pulmonary inflammation disorder. ALI is characterized by the marring of pulmonary endothelial and epithelial barriers and formation of proteinaceous fluid within the alveolar cavity. Figure 1 provides are visual aid for the effects of ALI. A number of insults have been documented as predominant causes of ALI. Those causes include lung infection, aspiration of toxins, sepsis, and trauma. If untreated, ALI progresses into an acute respiratory distress syndrome. ARDS is the fatally potential failure of the respiratory system as a result of lung injury from an array of infiltrates. Based on previous research, ARDS is diagnosed with the evidence of intensive marring of alveolar cavities, excessive leakage from alveoli-capillary network beds, and substantial accumulation of proteinaceous. Widely accepted, the American-European Consensus Conference (AECC) proposed definition of ARDS has been marked the diagnosed tool for patient categorization and research. Despite clinical care, ARDS debilitates pulmonary function, hampers oxygen saturation of the blood, and assists in bilateral infiltration of endogenous substances. Just as ALI, the development of ARDS is primarily associated with sepsis, pneumonia, trauma with multiple transfusions along with a number of diagnosis. Though caused by a number of infliction, ARDS is the tremendous marring of the alveoloapillary barriers which permits the accumulation of protein-rich fluid in the alveolar cavities of the lungs. The dysfunctional alveolar-capillary network beds impede proper oxygen saturation of blood which renders the lung functionally disable. Since the lungs are the primary conveyer of oxygen throughout the bodies, hamper oxygen saturation deprives the organs and subsequently leads to organ failure or, worse, death. Methods and controls: 1. Culturing and passaging rat lung microvascular endothelial cells (RLMVEC); 2. Overexpressing NPR-A and NPR-C in RLMVEC; 3. Monitoring the barrier resistance of RLMVEC in response to thrombin; 4. Assessing the levels of intracellular cyclic adenosine phosphate (cAMP) of RLMVEC in response to forskolin. Results: 1. RLMVEC can be transduced to express NPR-C and NPR-A; 2. ANP’s activation of NPR-C does not enhance barrier function in response to thrombin induced barrier dysfunction; 3. ANP’s activation of NPR-C does not inhibit forskolin induced intracellular cyclic adenosine monophosphate production. Conclusion and Future Directions: 1. Conducting additionally cAMP assays highlighting the biological effects of NPR-C and NPR-A; 2. Silencing the expression of NPR-C in vivo; 3. Breeding mice with a silenced expression of NPR-C.
Funder Acknowledgement(s): NIH R25 HL088992; NIH R01 HL123965; HHSN268201300048C.
Faculty Advisor: Elizabeth Harri, email@example.com
Role: I conducted experiments and data analysis underneath Elizabeth Harrington and Huetran Duong of Brown University.