Interfacial Macromolecular Transport and Metabolism of LDL  in the Arterial Intima
{'Code': '07020000', 'Directorate': {'Abbreviation': 'ENG', 'LongName': 'Directorate For Engineering'}, 'Division': {'Abbreviation': 'CBET', 'LongName': 'Div Of Chem, Bioeng, Env, & Transp Sys'}}
{'SignBlockName': 'Jeffrey Foltz', 'PO_EMAI': 'jfoltz@nsf.gov', 'PO_PHON': '7032924231'}
In this proposal, a new hypothesis is advanced for the local                    origin of atherogenesis which attempts to relate local changes in               macromolecular permeability to the detailed sequence of events                  and mechanisms leading to the formation of the foam cell lesion.  The           hypothesis offers a possible explanation for the relationship between           arterial wall cell turnover, macromolecular permeability, the receptor          mediated metabolism of the cellular component of the arterial intima            and media, the recruitment and subendothelial                                   penetration and transport of blood borne monocytes and their                    conversion to macrophage type foam cells.  The time dependent                   model developed by the principal investigators to show the                      quantitative relationship between endothelial macromolecular                    permeability and leaky junctions associated with statistically                  infrequent cells in turnover will be further developed to                       include:  (1) a discrete diffusion barrier for the internal                     elastic lamina, (2) convection in the interendothelial clefts and               subendothelial tissue and (3) models for the receptor mediated                  low density lipoprotein (LDL) metabolism of the endothelial and                 smooth muscle cells.  The quantitative models in (3) will be                    based on the experimental model of Brown and Goldstein for the                  LDL receptor mediated metabolism and the intracellular regulation of            their number density in human fibroblasts.  Simplified                          mathematical models have been formulated for the six key                        processes governing this regulation wherein the constants in the                individual processes are determined from available experiments.                 The objective of these models is to obtain a quantitative                       predictive relationship between the extracellular native LDL                    concentration, the hydrolyzed free cholesterol content of the                   cells and the regulation of receptor number.  The subendothelial                LDL concentration predicted by the overall model is then related                to the release of chemotactic factors for the recruitment and                   adhesion of blood borne monocytes based on the quantitative                     criteria proposed in the new hypothesis.  Experiments conducted                 in a complementary NIH grant have recently confirmed the first                  part of the hypothesis showing that the leakage of LDL across the               endothelium does occur via poorly formed junctions surrounding                  the small population of cells in turnover.  Further experiments                 are required to validate the quantitative link between                          subendothelial LDL levels and monocyte recruitment proposed in                  the new hypothesis.
[{'FirstName': 'Peter', 'LastName': 'Ganatos', 'PI_MID_INIT': None, 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Peter Ganatos', 'EmailAddress': None, 'NSF_ID': '000177251', 'StartDate': '08/01/1988', 'EndDate': None, 'RoleCode': 'Co-Principal Investigator'}, {'FirstName': 'Robert', 'LastName': 'Robert', 'PI_MID_INIT': None, 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Robert Robert', 'EmailAddress': None, 'NSF_ID': '000182870', 'StartDate': '08/01/1988', 'EndDate': None, 'RoleCode': 'Co-Principal Investigator'}, {'FirstName': 'Sheldon', 'LastName': 'Weinbaum', 'PI_MID_INIT': None, 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Sheldon Weinbaum', 'EmailAddress': 'weinbaum@ccny.cuny.edu', 'NSF_ID': '000171145', 'StartDate': '08/01/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}]
{'Name': 'CUNY City College', 'CityName': 'NEW YORK', 'ZipCode': '100319101', 'PhoneNumber': '2126505418', 'StreetAddress': '160 CONVENT AVE', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'New York', 'StateCode': 'NY', 'CONGRESSDISTRICT': '13', 'CONGRESS_DISTRICT_ORG': 'NY13', 'ORG_UEI_NUM': 'L952KGDMSLV5', 'ORG_LGL_BUS_NAME': 'RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK', 'ORG_PRNT_UEI_NUM': None}
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{'Code': '141400', 'Text': 'INTERFAC PROCESSES & THERMODYN'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8803116.xml'}