A5029379615- Pregnancy-related medical research
- Injury Epidemiology and Prevention
- Neonatal Respiratory Health Research
- Occupational Health and Performance
- Asthma and respiratory diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Mesenchymal stem cell research
- Pelvic and Acetabular Injuries
- Cardiac Fibrosis and Remodeling
- Hormonal Regulation and Hypertension
- Tissue Engineering and Regenerative Medicine
- Birth, Development, and Health
- Nitric Oxide and Endothelin Effects
- Pregnancy and preeclampsia studies
- Immune cells in cancer
- Atherosclerosis and Cardiovascular Diseases
- Human Health and Disease
- Inhalation and Respiratory Drug Delivery
- Pleural and Pulmonary Diseases
- Renal and related cancers
- Atrial Fibrillation Management and Outcomes
- Cardiovascular Disease and Adiposity
- Renin-Angiotensin System Studies
- Preterm Birth and Chorioamnionitis
- Pulmonary Hypertension Research and Treatments
The University of Melbourne
2011-2024
Monash University
2015-2024
Australian Regenerative Medicine Institute
2015-2024
RELX Group (United States)
2022
ORCID
2021
Discovery Institute
2016-2019
Monash Health
2015-2018
Florey Institute of Neuroscience and Mental Health
2007-2016
Jagiellonian University
2015
British Heart Foundation
2015
Renal inflammation, leading to fibrosis and impaired function is a major contributor the development of hypertension. The NLRP3 inflammasome mediates inflammation in several chronic diseases by processing cytokines pro-interleukin (IL)-1β pro-IL-18. In this study, we investigated whether MCC950, recently-identified inhibitor activity, reduces blood pressure (BP), renal dysfunction mice with established C57BL6/J were made hypertensive uninephrectomy treatment deoxycorticosterone acetate (2.4...
Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in remains unknown. We investigated mice B-cell activation and production moreover B-cell/IgG deficiency affords protection against vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was (1) a 25% increase the proportion of splenic B cells expressing marker CD86, (2) an 80% plasma cell numbers, (3) 500% circulating IgG, (4) marked accumulation...
We have identified a novel human relaxin gene, designated H3 relaxin, and an equivalent gene in the mouse from Celera Genomics data base. Both genes encode putative prohormone sequence incorporating classic two-chain, three cysteine-bonded structure of relaxin/insulin family and, importantly, contain RXXXRXX(I/V) motif B-chain that is essential for receptor binding. A peptide derived likely proteolytic processing was synthesized found to possess activity bioassays utilizing monocytic cell...
Cardiac fibrosis is a key component of heart disease and involves the proliferation differentiation matrix-producing fibroblasts. The effects an antifibrotic peptide hormone, relaxin, in inhibiting this process were investigated. We used rat atrial ventricular fibroblasts, which respond to profibrotic stimuli express relaxin receptor (LGR7), addition two vivo models cardiac fibrosis. when plated at low density or stimulated with TGF-β angiotensin II (Ang II), accelerated fibroblast into...
There is some evidence, mainly from rodent studies, that any factor which alters the final total number of nephrons formed, during nephrogenesis, will result in hypertension adult life. Sheep, programmed to become hypertensive by exposure synthetic glucocorticoid (dexamethasone, 0.48 mg h-1, for 48 h) early development (~27 days gestation), were killed at 7 years age, and had nephron counting performed unbiased stereology. Mean arterial pressure was 83 +/- 4 mmHg dexamethasone (DEX) group (n...
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The antifibrotic effects of the peptide hormone relaxin on cardiac and renal fibrosis were studied in 9- to 10-month-old male spontaneously hypertensive rats (SHR) normotensive Wistar-Kyoto (WKY). Rats (n=8 9 per group) allocated into 3 groups: WKY controls, vehicle-treated SHR (SHR-V), relaxin-treated (SHR-R). Relaxin (0.5 mg/kg day) was administered via subcutaneously implanted osmotic mini-pumps over 2 weeks before hearts kidneys harvested for analysis. Collagen content analyzed by...
Aims Elevated blood pressure (EBP) is the most prevalent and potentially modifiable risk factor for AF, yet little known of its atrial effects. We aimed to characterize electrical structural changes in a chronic ovine model EBP after prenatal corticosteroid exposure. Methods results Twelve sheep with chronically (mean arterial 94±3 mmHg) six controls (71±4 mmHg, P<0.01) underwent acute open chest electrophysiologic pathologic studies. measured refractoriness at appendages 3 cycle lengths...
Background and Purpose Inflammasomes are multimeric complexes that facilitate caspase‐1‐mediated processing of the pro‐inflammatory cytokines IL ‐1β ‐18. Clinical hypertension is associated with renal inflammation elevated circulating levels Therefore, we investigated whether in mice increased expression and/or activation inflammasome kidney, if inhibition activity reduces BP , markers fibrosis. Experimental Approach Wild‐type inflammasome‐deficient ASC −/− were uninephrectomized received...
Chronic liver injury and inflammation lead to hepatic fibrosis, cirrhosis, failure. Embryonic mesenchymal stem cells have been shown reduce experimental fibrosis but potential limitations, including the formation of dysplastic precursors, tumors, profibrogenic cells. Other stem-like may without tumor cell formation. To test this hypothesis we transplanted human amnion epithelial (hAEC), isolated from term delivered placenta, into immunocompetent C57/BL6 mice at week 2 a 4-week regimen carbon...
The relationship between airway inflammation and structural changes of remodeling, their relative effects on function, are poorly understood. Remodeling is thought to result from chronic repetitive injury the wall caused by inflammation; however, mechanisms regulating remodeling have not been clearly defined. We examined sequence events in using three commonly used mouse models allergic airways disease which mice exposed nebulized ovalbumin for four consecutive days (acute), seven...
Macrophages accumulate in blood vessels during hypertension. However, their contribution to vessel remodeling is unknown. In the present study, we examined polarization state of macrophages (M1/M2) aortas mice hypertension and investigated whether antagonism chemokine receptors involved macrophage accumulation reduces pressure (BP). Mice treated with ANG II (0.7 mg·kg −1 ·day , 14 days) had elevated systolic BP (158 ± 3 mmHg) compared saline-treated animals (122 mmHg). Flow cytometry...
The hormone, relaxin, inhibits aberrant myofibroblast differentiation and collagen deposition by disrupting the TGF-β1/Smad2 axis, via its cognate receptor, Relaxin Family Peptide Receptor 1 (RXFP1), extracellular signal-regulated kinase (ERK)1/2 phosphorylation (pERK) a neuronal nitric oxide (NO) synthase (nNOS)-NO-cyclic guanosine monophosphate (cGMP)-dependent pathway. However, signalling pathways involved in additional ability to increase matrix metalloproteinase (MMP) expression...
Mesenchymal stem cells (MSCs) ameliorate injury and accelerate repair in many organs, including the kidney, although reparative mechanisms interaction with macrophages have not been elucidated. This study investigated potential of human bone marrow-derived MSCs traced their homing patterns following administration to mice ischemia-reperfusion (IR) using whole body bioluminescence imaging. The effect on macrophage phenotype direct indirect coculture was assessed qPCR. Human cytokine...
Lung diseases are a major cause of global morbidity and mortality that treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models lung disease. However, there limitations the translation these clinical Studies delayed treatment does not improve outcomes do reflect repeated injury is present in most diseases. We tested efficacy amnion mesenchymal cells (AM-MSC), bone marrow MSC (BM-MSC) human amniotic epithelial (hAEC) C57BL/6 mice using...
Relaxin is a naturally occurring peptide hormone that mediates systemic hemodynamic and renal adaptive changes during pregnancy abrogates aberrant scar tissue formation (fibrosis) in diverse pathogeneses. However, its efficacy relative to renin–angiotensin system blockade, the most effective antifibrotic strategy currently available, not known. We compared individual versus combined effects of serelaxin (a recombinant form human gene-2 relaxin) angiotensin-converting enzyme inhibitor...