Biomedical subjects

Xiao-Lei Moore

Publications and source records attributed to Xiao-Lei Moore.

4 recordsLinked to original sources

PubMed2006

Transgenic alpha1A-adrenergic activation limits post-infarct ventricular remodeling and dysfunction and improves survival.

OBJECTIVE: Myocardial contractility is enhanced in transgenic (TG) mice with cardiac-restricted overexpression of the alpha1A-adrenergic receptors (alpha1A-AR). We tested the hypothesis that this enhanced inotropy protects against dysfunction and remodeling after myocardial infarction (MI). METHODS: We subjected alpha1A-TG and non-TG mice (NTG) to MI and determined changes in left ventricular (LV) function and diastolic dimension (LVDd) by echocardiography prior to and at 1, 3, 7, 12 and 15 weeks thereafter. RESULTS: Although infarct size was similar in the NTG and alpha1A-TG groups (32+/-2 vs. 29+/-2% of LV, P=NS), mortality due to heart failure was lower after MI in the alpha1A-TG (37%, n=39) than that in the NTG animals (63%, n=56, P=0.026). NTG and alpha1A-TG mice showed similar reductions in LV fractional shortening (FS) and increases in LVDd at week-1 after MI. However, whereas NTG mice showed continuous deterioration over a 15-week period after MI in FS (fell by 40%, from 30+/-2 to 18+/-1%, P<0.01) and LVDd (increased by 24%, from 4.2+/-0.1 to 5.2+/-0.1 mm, P<0.01), the changes in both FS (fell by 14%, from 42+/-2 to 36+/-2%) and LVDd (increased by 8%, from 3.8+/-0.1 to 4.1+/-0.1 mm, both changes P<0.01 vs. NTG) were significantly less severe in the alpha1A-TG mice and did not progress after 3 weeks. At 15 weeks after MI, LV catheterization revealed better preservation of dP/dtmax in the alpha1A-TG vs. NTG mice (7270+/-324, vs. 5938+/-372 mmHg/s, P<0.05). CONCLUSION: Enhanced inotropy resulting from transgenic overexpression of alpha1A-AR is well maintained chronically after MI and limits echocardiography-determined LV remodeling, preserves function, and reduces acute heart failure death.

Actins↗

PubMed2006

Adult bone marrow cells differentiate into neural phenotypes and improve functional recovery in rats following traumatic brain injury.

This study aims to investigate the therapeutic potential of adult bone marrow stromal cells (BMSCs). Exposed to a cocktail of induction medium, some BMSCs could differentiate into cell types with phenotypes of neural lineages in vitro. These cells expressed neural markers nestin, GFAP, 68-kDa neurofilament and beta-tubulin III as detected by immunohistochemistry and RT-PCR. Fluorescence-labeled cells were injected intravenously at 72 h after traumatic brain injury. Transplanted cells survived and migrated to the ipsilateral cerebral cortex at different time points after injection. They were immunopositive for neuronal marker MAP-2, oligodendrocyte marker CNPase, astrocytic maker GFAP or microglial marker OX-42 in vivo. In rats receiving BMSC transplants, there were significant improvements in motor and neurological functions when compared with the control groups. Hence, the therapeutic potential of BMSCs for traumatic brain injury is further amplified.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed2006

Inhibition of mTOR reduces chronic pressure-overload cardiac hypertrophy and fibrosis.

BACKGROUND AND OBJECTIVE: Inhibition of established left ventricular hypertrophy (LVH) and fibrosis may bring clinical benefits by reducing cardiac morbidity and mortality. The mammalian target of rapamycin, mTOR, is known to play a critical role in determining cell and organ size. We investigated whether mTOR inhibition can inhibit the chronic pressure-overload-induced LVH and fibrosis. METHODS: Male FVB/N mice underwent transverse aortic constriction (TAC) for 5 weeks to allow for establishment of LVH, followed by treatment with the mTOR inhibitor, Rapamune (2 mg/kg per day, gavage), for 4 weeks. Echocardiography was used to monitor changes in LVH and function. Haemodynamic, morphometric, histological and molecular analyses were conducted. RESULTS: Inhibition of mTOR by Rapamune was confirmed by a suppression of activated phosphorylation of ribosomal S6 protein and eukaryotic translation initiation factor-4E due to pressure overload. Despite a comparable degree of pressure overload between the vehicle- or Rapamune-treated TAC groups, Rapamune treatment for 4 weeks attenuated TAC-induced LVH by 46%, estimated by LV weight or myocyte size, and LV fractional shortening was also preserved versus vehicle-treated control (39 +/- 1 versus 32 +/- 2%, P < 0.05). Inhibition of established LVH by Rapamune was associated with a 38% reduction in collagen content. Moreover, altered gene expression due to pressure overload was largely restored. CONCLUSION: Despite sustained pressure overload, inhibition of mTOR by a 4-week period of Rapamune treatment attenuates chronically established LVH and cardiac fibrosis with preserved contractile function.

Analysis of Variance↗

PubMed2005

Regression of pressure overload-induced left ventricular hypertrophy in mice.

As a prelude to investigating the mechanism of regression of pressure overload-induced left ventricular (LV) hypertrophy (LVH), we studied the time course for the development and subsequent regression of LVH as well as accompanying alterations in cardiac function, histology, and gene expression. Mice were subjected to aortic banding for 4 or 8 wk to establish LVH, and regression was initiated by release of aortic banding for 6 wk. Progressive increase in LV mass and gradual chamber dilatation and dysfunction occurred after aortic banding. LVH was also associated with myocyte enlargement, interstitial fibrosis, and enhanced expression of atrial natriuretic peptide, collagen I, collagen III, and matrix metalloproteinase-2 but suppressed expression of alpha-myosin heavy chain and sarcoplasmic reticulum Ca(2+)-ATPase. Aortic debanding completely or partially reversed LVH, chamber dilatation and dysfunction, myocyte size, interstitial fibrosis, and gene expression pattern, each with a distinct time course. The extent of LVH regression was dependent on the duration of pressure overload, evidenced by the fact that restoration of LV structure and function was complete in animals subjected to 4 wk of aortic banding but incomplete in animals subjected to 8 wk of aortic banding. In conclusion, LVH regression comprises a variety of morphological, functional, and genetic components that show distinct time courses. A longer period of pressure overload is associated with a slower rate of LVH regression.

Animals↗