A5011561996- Atherosclerosis and Cardiovascular Diseases
- Pregnancy and preeclampsia studies
- Birth, Development, and Health
- Bone and Dental Protein Studies
- Cell Adhesion Molecules Research
- Gestational Diabetes Research and Management
- Hormonal Regulation and Hypertension
- Lipoproteins and Cardiovascular Health
- Folate and B Vitamins Research
- Congenital heart defects research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Phagocytosis and Immune Regulation
- Connective tissue disorders research
- Genetic Associations and Epidemiology
- Genetic Mapping and Diversity in Plants and Animals
- Proteoglycans and glycosaminoglycans research
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- Heme Oxygenase-1 and Carbon Monoxide
- Signaling Pathways in Disease
- Cardiac Fibrosis and Remodeling
- Protease and Inhibitor Mechanisms
- Apelin-related biomedical research
- Renin-Angiotensin System Studies
- Microbial metabolism and enzyme function
University of North Carolina at Chapel Hill
2013-2025
University of North Carolina Health Care
2017
Lysyl hydroxylase 2 (LH2) is a member of LH family that catalyzes the hydroxylation lysine (Lys) residues on collagen, and this particular isozyme has been implicated in various diseases. While its function as telopeptidyl generally accepted, several fundamental questions remain unanswered: 1. Does LH2 catalyze all Lys collagen? 2. Is involved helical hydroxylation? 3. What are functional consequences when completely absent? To answer these questions, we generated LH2-null MC3T3 cells...
To uncover the potential cardiovascular effects of human polymorphisms influencing transforming growth factor β1 (TGFβ1) expression, we generated mice with Tgfb1 mRNA expression graded in five steps from 10% to 300% normal. Adrenal genes for mineralocorticoid-producing enzymes ranged 50% normal hypermorphs at age 12 wk 400% hypomorphs accompanied proportionate changes plasma aldosterone levels, whereas volumes 150% by marked compensatory angiotensin II and renin levels. The aldosterone/renin...
Covalent intermolecular cross-linking of collagen is essential for tissue stability. Recent studies have demonstrated that cyclophilin B (CypB), an endoplasmic reticulum (ER)-resident peptidyl-prolyl cis-trans isomerase, modulates lysine (Lys) hydroxylation type I impacting chemistry. However, the extent modulation, molecular mechanism and functional outcome in tissues are not well understood. Here, we report that, CypB null (KO) mouse skin, two unusual cross-links lacking Lys formed while...
Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood. To investigate the function of this modification bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) which Glt25d1 gene expression was stably suppressed. In Sh GLT25D1 protein levels were markedly diminished comparison to controls (MC those transfected with empty...
Preeclampsia is a complex pregnancy-related hypertensive disorder which poses significant risks for both maternal and fetal health. affects 5-8% of the pregnancies in United States, causing public health economic burden. Despite extensive research, etiology pathogenesis preeclampsia remain elusive, but have been correlated with conditions such as obesity. In past decades, incidence increased along prevalence obesity among women reproductive age. Maternal has shown to negatively affect...
The genetic background of apolipoprotein E (apoE) deficient mice influences atherosclerotic plaque development. We previously reported three quantitative trait loci (QTL), Aath1–Aath3, that affect aortic arch atherosclerosis independently those in the root a cross between C57BL6 apoEKO (B6-apoE) and 129S6 (129-apoE). To gain further insight into factors influence at different vascular locations, we analyzed 335 F2 from an intercross 129-apoE on DBA/2J (DBA-apoE). extent was very similar two...
Arch atherosclerosis 4 (Aath4) is a quantitative trait locus for atherosclerotic plaque formation in the inner curve of aortic arch previously identified an F2 cross Apoe-/- mice on DBA/2J and 129S6 backgrounds. C-mer proto-oncogene tyrosine kinase (Mertk), coding ligand-activated transmembrane kinase, candidate gene within same chromosomal region. Our objective was to determine whether strain differences Mertk influence formation.To dissect effects atherosclerosis, we first established...
Apolipoprotein E-null mice on a DBA/2J genetic background (DBA-apoE) are highly susceptible to atherosclerosis in the aortic root area compared with those 129S6 (129-apoE). To explore atherosclerosis-responsible regions, we performed quantitative trait locus (QTL) analysis using 172 male and 137 female F2 derived from an intercross between DBA-apoE 129-apoE mice. A genome-wide scan identified two significant QTL for size of lesions at root: one is Ath44 Chromosome (Chr) 1 158 Mb, other Ath45...
Engulfment and cell motility protein 1 (ELMO1) is part of a guanine nucleotide exchange factor for Ras-related C3 botulinum toxin substrate (Rac), ELMO1 polymorphisms were identified to be associated with diabetic nephropathy in genome-wide association studies. We generated set Akita Ins2C96Y mice having 5 graded cardiac mRNA levels from 30% 200% normal found that severe dilated cardiomyopathy develops ELMO1-hypermorphic independent renal function at age 16 weeks, whereas ELMO1-hypomorphic...
We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe-/- mice DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 was associated with smaller plaque size. One of candidate genes underlying Stabilin-2 (Stab2), which encodes clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, role Stab2 is unknown....
Abstract Stabilin2 ( Stab2 ) encodes a large transmembrane protein which is predominantly expressed in the liver sinusoidal endothelial cells (LSECs) and functions as scavenger receptor for various macromolecules including hyaluronans (HA). In DBA/2J mice, plasma HA concentration ten times higher than 129S6 or C57BL/6J this phenotype genetically linked to locus. mRNA LSECs was significantly lower 129S6, leading reduced STAB2 proteins LSECs. We found retrovirus-derived transposable element,...
Obesity is a risk factor for preeclampsia. We investigated how obesity influences preeclampsia in mice lacking ankyrin-repeat-and-SOCS-box-containing-protein 4 (ASB4), which promotes trophoblast differentiation via degrading the inhibitor of DNA-binding protein 2 (ID2). Asb4-/- on normal chow (NC) develop mild preeclampsia-like phenotypes during pregnancy, including hypertension, proteinuria, and reduced litter size. Wild-type (WT) females were placed high-fat diet (HFD) starting at weaning....
Quantitative trait locus (QTL) analyses of intercross populations between widely used mouse inbred strains provide a powerful approach for uncovering genetic factors that influence susceptibility to atherosclerosis. Epistatic interactions are common in complex phenotypes and depend on backgrounds. To dissect architecture atherosclerosis, we analyzed F2 progeny from cross apolipoprotein E-null mice DBA/2J (DBA-apoE) C57BL/6J (B6-apoE) backgrounds compared the results with those two previous...
Vitamin B12 (B12) is an essential co-factor for two enzymes in mammalian metabolism and can also act as a mimetic of superoxide dismutase (SOD) converting (O2 •−) to hydrogen peroxide (H2O2). High oral dose decreases renal O2 •− post-ischemia/reperfusion injury mice protects against damage induced by hypoxia/reperfusion mouse kidney proximal tubular cells (BU.MPT). unstable rapidly converted H2O2. H2O2 mediates oxidative stress associated with •−. Whether unknown. Both BU.MPT brain...
Introduction: In preeclampsia (PE), impaired trophoblast proliferation and differentiation are thought to cause abnormal placentation subsequent clinical manifestations of the disease—i.e., hypertension, proteinuria, end-organ damage. Insulin-like growth factor 1 (IGF-1) influences cell function, however mechanisms IGF-1’s action on trophoblasts is not well understood. Inhibitor DNA binding protein 2 (ID2) involved in implicated many processes disrupted PE including placental development,...
In preeclampsia (PE), impaired trophoblast proliferation and differentiation are thought to cause abnormal placentation subsequent clinical manifestations of the disease, i.e., hypertension, proteinuria, end-organ damage. Insulin-like growth factor-1 (IGF-1) influences cell function; however, mechanism IGF-1’s action on trophoblasts is not understood well. Inhibitor DNA binding protein 2 (ID2) involved in implicated many processes disrupted PE, including placental development, vascular...