Abstract: SR-BI is present at relatively high levels on the membranes of hepatocytes and steroidogenic tissues, including the adrenal gland, testes, and ovaries, where it mediates the uptake and transport of cholesteryl ester from high density lipoproteins. It has been demonstrated that transgenic animals which do not produce SR-BI are healthy, with the exception that the females are infertile. SR-BI KO females have abnormal HDLs, ovulate dysfunctional oocytes and are infertile. Surgical, genetic and pharmacologic methods were used to show that the fertility of SR-BI KO females (or their transplanted oocytes) can be restored in the absence of ovarian and/or extraovarian SR-BI expression by manipulations that modify the structure, composition and/or abundance of their abnormal plasma lipoproteins. These manipulations included inactivation of the apolipoprotein A-I gene and administration of the cholesterol-lowering drug PROBUCOL™.

Abstract: Methods for regulation of lipid and cholesterol uptake are described which are based on regulation of the expression or function of the SR-BI HDL receptor. The examples demonstrate that estrogen dramatically downregulates SR-BI under conditions of tremendous upregulation of the LDL-receptor. The examples also demonstrate the upregulation of SR-BI in rat adrenal membranes and other non-placental steroidogenic tissues from animals treated with estrogen, but not in other non-placental non-steroidogenic tissues, including lung, liver, and skin. Examples further demonstrate the uptake of fluorescently labeled HDL into the liver cells of animal, which does not occur when the animals are treated with estrogen. Examples also demonstrate the in vivo effects of SR-BI expression on HDL metabolism, in mice transiently overexpressing hepatic SR-BI following recombinant adenovirus infection. overexpression of the SR-BI in the hepatic tissue caused a dramatic decrease in cholesterol blood levels.

Abstract: Transgenic animals that do not express functional SR-BI and ApoE develop severe atherosclerosis, by age four weeks in transgenic mice. Moreover, these animals exhibit progressive heart dysfunction by as early as age four weeks, and die by age nine weeks. This animal model has now been demonstrated to be useful as a screen for compounds which alleviate the symptoms of atherosclerosis and heart disease. Animals (Apo E−/− SR-BI +/−) were fed PROBUCOL beginning at the time of mating. Offspring are weaned at three weeks and fed PROBUCOL. In contrast to animals (Apo E−/− SR-BI −/−) not fed PROBUCOL, 50% of whom are dead at six weeks, all animals (Apo E−/− SR-BI −/−) on PROBUCOL have a normal phenotype (MRI of heart function, ECG, echocardiogram, histology) at six weeks. At seven to eight months, there is evidence of atherosclerosis and some myocardial infarction. This demonstrates that the compound has a preventative action.

Abstract: The present invention provides reagents, kits and methods for identifying and characterizing interactions between proteins and/or polypeptides. The inventive system and methods allow analysis of these interactions in vivo in eukaryotic systems, including mammalian systems. Advantages provided by various embodiments of the inventive system and methods as compared with other systems and methods for analyzing interactions between proteins or polypeptides, such as the yeast two-hybrid system, include (i) reduced ambiguity associated with identification of a potential interaction; (ii) ability to identify or study interactions that occur outside the nucleus; (iii) absence of reliance on reporter genes; and/or (iv) ability to study interactions with polypeptides that have transcriptional activation activity.

Abstract: Transgenic animals that do not express functional SR-BI and ApoE develop severe atherosclerosis, by age four weeks in transgenic mice. Moreover, these animals exhibit progressive heart block by age four weeks, and die by age nine weeks. Pathology shows extensive fibrosis of the heart and occlusion of coronary arteries. The occlusion appears to be due to clotting, since fat deposition is in the walls. These animals are good models for the following diseases, and for screening of drugs useful in the treatment and/or prevention of these disorders: cardiac fibrosis, myocardial infarction, defects in electrical conductance, atherosclerosis, unstable plaque, and stroke. In contrast to other known models for atherosclerosis, these animals do not have to be fed extreme diets for long periods before developing atherosclerosis. No other known model for heart attacks and stroke is known.

Abstract: Transgenic animals that do not express functional SR-BI and ApoE develop severe atherosclerosis, by age four weeks in transgenic mice. Moreover, these animals exhibit progressive heart block by age four weeks, and die by age nine weeks. Pathology shows extensive fibrosis of the heart and occlusion of coronary arteries. The occlusion appears to be due to clotting, since fat deposition is in the walls. These animals are good models for the following diseases, and for screening of drugs useful in the treatment and/or prevention of these disorders: cardiac fibrosis, myocardial infarction, defects in electrical conductance, atherosclerosis, unstable plaque, and stroke. In contrast to other known models for atherosclerosis, these animals do not have to be fed extreme diets for long periods before developing atherosclerosis. No other known model for heart attacks and stroke is known.

Abstract: Two distinct scavenger receptor type proteins having high affinity for modified lipoproteins and other ligands have been isolated, characterized and cloned. HaSR-BI, an AcLDL and LDL binding scavenger receptor, which is distinct from the type I and type II macrophage scavenger receptors, has been isolated and characterized and DNA encoding the receptor cloned from a variant of Chinese Hamster Ovary Cells, designated Var-261. dSR-CI, a non-mammalian AcLDL binding scavenger receptor having high ligand affinity and broad specificity, was isolated from Drosophila melanogaster. The isolated receptors are useful in screening for drugs that inhibit uptake of cholesterol in endothelial or adipose cells or macrophages, respectively. They are also useful as probes for the isolation of other lipoprotein receptors and in research the roles of these receptors.

Abstract: SR-BI is present on the membranes of hepatocytes and steroidogenic tissues, including the adrenal gland, testes, and ovaries, where it mediates the uptake and transport of cholesteryl ester from high density lipoproteins. It has been demonstrated that transgenic animals which do not produce SR-BI are perfectly healthy, with the exception that the females are infertile. This provides evidence that inhibition of uptake, binding or transport of cholesteryl ester to SR-BI can be used to inhibit pregnancy. The same pathway can also be used to decrease production of steroids, and therefore be used as a therapy for disorders involving steroidal overproduction.

Abstract: Two distinct scavenger receptor type proteins having high affinity for modified lipoproteins and other ligands have been isolated, characterized and cloned. HaSR-BI, an AcLDL and LDL binding scavenger receptor, which is distinct from the type I and type II macrophage scavenger receptors, has been isolated and characterized and DNA encoding the receptor cloned from a variant of Chinese Hamster Ovary Cells, designated Var-261. dSR-CI, a non-mammalian AcLDL binding scavenger receptor having high ligand affinity and broad specificity, was isolated from Drosophila melanogaster. The isolated receptors are useful in screening for drugs that inhibit uptake of cholesterol in endothelial or adipose cells or macrophages, respectively. They are also useful as probes for the isolation of other lipoprotein receptors and in research the roles of these receptors.

Abstract: Methods for regulation of lipid and cholesterol uptake are described which are based on regulation of the expression or function of the SR-BI HDL receptor. The examples demonstrate that estrogen dramatically downregulates SR-BI under conditions of tremendous upregulation of the LDL-receptor. The examples also demonstrate the upregulation of SR-BI in rat adrenal membranes and other non-placental steroidogenic tissues from animals treated with estrogen, but not in other non-placental non-steroidogenic tissues, including lung, liver, and skin. Examples further demonstrate the uptake of fluorescently labeled HDL into the liver cells of animal, which does not occur when the animals are treated with estrogen. Examples also demonstrate the in vivo effects of SR-BI expression on HDL metabolism, in mice transiently overexpressing hepatic SR-BI following recombinant adenovirus infection. Overexpression of the SR-BI in the hepatic tissue caused a dramatic decrease in cholesterol blood levels.

Abstract: Methods for regulation of lipid and cholesterol uptake are described which are based on regulation of the expression or function of the SR-BI HDL receptor. The examples demonstrate that estrogen dramatically downregulates SR-BI under conditions of tremendous upregulation of the LDL-receptor. The examples also demonstrate the upregulation of SR-BI in rat adrenal membranes and other non-placental steroidogenic tissues from animals treated with estrogen, but not in other non-placental non-steroidogenic tissues, including lung, liver, and skin. Examples further demonstrate the uptake of fluorescently labeled HDL into the liver cells of animal, which does not occur when the animals are treated with estrogen.

Abstract: Macrophage scavenger receptor protein or active fragments thereof bind specifically to the lipoteichoic acid residues on the Gram-positive bacterial cell wall. This protein or active fragments thereof can be used in a variety of methods including methods to specifically purify lipoteichoic acid, to preferentially label or detect lipoteichoic acid or lipoteichoic acid-containing compounds or cells, and to treat patients having Gram-positive bacterial infections such as septicemia and associated pathophysiological states such as septic shock.

Abstract: A substantially pure receptor protein capable of binding acetylated low density lipoprotein and oxidized low density lipoprotein is disclosed herein. This protein is characterized by having a molecular weight of about 220,000 daltons, and an affinity for oxidized low density lipoprotein and acetylated low density lipoprotein. Further, it is an integral membrane protein which includes a collagen domain. Proteins having an affinity for the receptor protein as well as DNA sequences encoding at least a portion of the receptor protein are also disclosed herein. In addition, devices for purification purposes and methods for detecting atherosclerotic plaques are described, both of which utilize the receptor protein or binding proteins thereto.