Biomedical subjects

Fanglin Lu

Publications and source records attributed to Fanglin Lu.

9 recordsLinked to original sources

PubMed2026

Development of Electrocardiography Standards for Evaluating Myocardial Infarction and Ischemia-Reperfusion Injury in Mice.

BACKGROUND: Acute and chronic heart failure secondary to myocardial infarction (MI) and cardiac ischemia-reperfusion injury (IRI) are leading causes of death in ischemic heart disease. A mouse model is indispensable for investigating MI and IRI, and the development of reliable mouse MI and IRI models is essential for advancing research in this field. The clear early diagnostic criteria for confirming successful induction of MI and IRI in mice remain lacking. METHODS: Adult C57BL/6J background mice underwent left anterior descending coronary artery ligation to induce acute MI, or ligation followed by reperfusion to induce IRI. The success of the MI and IRI model establishment was confirmed by 2,3,5-triphenyltetrazolium chloride staining and echocardiography. Electrocardiography was used to monitor the electric activity in the mice. CONCLUSIONS: Electrocardiography demonstrated that ST-segment elevation in ECG lead II and corrected QTc interval prolongation at 30 minutes following left anterior descending ligation as 2 key early indicators of successful MI. Echocardiography analysis revealed that the magnitude of ST-segment elevation strongly correlated with the left anterior descending ligation site, where a more proximal ligation produced a greater ST-segment elevation amplitude and more severe ischemia. In IRI models, ST-segment elevation typically resolved and returned to baseline within 20 minutes of reperfusion. This study developed quantifiable early diagnostic criteria for successful MI and IRI induction based on characteristic ECG changes. These quantifiable ECG parameters provide early diagnostic standards that can significantly streamline and optimize modeling procedures.

Animals↗

PubMed2007

Identification of genes differentially regulated by transcription factor, AP-2delta.

In an effort to better understand the transcriptional program regulated by transcription factor, AP-2delta, we used cDNA microarray to evaluate the relative expression of human genes in AD293 cells by exogenous expression of AP-2delta. Microarray showed 29 genes that were up-regulated and 39 genes with a down-regulated expression pattern. Among the identified genes were those encoding transcription factors, signal transduction molecules, kinases, as well as genes regulating cell growth, differentiation, and cell adhesion, a set of genes suggested to be regulated by AP-2. The results of microarray was validated for some regulated genes by real-time PCR analysis. These observations shed novel insight into the mechanism of AP-2delta action and provide a range of target genes for further investigation.

Binding Sites↗

PubMed2006

Dual specificity phosphotase 18, interacting with SAPK, dephosphorylates SAPK and inhibits SAPK/JNK signal pathway in vivo.

The SAPK/JNKs play important roles in numerous cellular processes, and for this reason they have become putative drug targets. Most dual-specificity protein phosphatases (DSPs) play important roles in the regulation of mitogenic signal transduction and cell cycle control in response to extracellular stimuli. Dual-specificity phosphatase 18 (DUSP18), a newly recognized SAPK/JNK phosphatase, is widely expressed. This expression is modulated in response to extracellular stimuli. By phosphorylation assay, pull down and coimmunoprecipitation experiments, it is shown here that DUSP18 interacts with SAPK/JNK and dephosphorylates it both in vitro and in vivo. DUSP18 does not dephosphorylate p38 or p44ERK1. Furthermore, DUSP18 inhibits SAPK/JNK pathway in vivo. Based on these findings, DUSP18 appears to serve an important role by regulation of SAPK/JNK pathway.

Blotting, Western↗

PubMed2003

Transplanted skeletal myoblasts can fully replace the infarcted myocardium when they survive in the host in large numbers.

BACKGROUND: It is not clear how many skeletal myoblasts (SM) can survive and exert beneficial effects in the host myocardial infarction (MI) area. We assessed the hypothesis that a large number of SM can replace the MI area with reverse left ventricular (LV) remodeling. METHODS AND RESULTS: MI was created by left coronary artery ligation in male Lewis rats. Four weeks after ligation, 45 rats had skeletal myoblast transplantation in the MI area. They were randomized into 3 groups according to the number of SM: group I (n=15), 5 x 10(7); group II (n=15), 5 x 10(6); and group III (n=15), 5 x 10(5) cells. Donor SM were obtained from neonatal Lewis rats and directly used without expansion. Another four weeks later, all rats were sacrificed following hemodynamic assessment. All heart sections were stained with anti-fast skeletal myosin heavy chain (FSMHC) antibody to determine the spacial extent of donor myocytes. RESULTS: Four weeks after transplantation, LV diastolic dimension was decreased, fractional area change was increased, and MI size was decreased maximally in group I. Histological study showed that donor cells positive for FSMHC occupied the MI area with nearly normal wall thickness in group I, in which estimated volume of donor-derived muscle tissue was 40 mm3. In the other groups, FSMHC-positive cells were found only partly in the MI area. CONCLUSIONS: A large number of freshly isolated neonatal SM can survive in the host and fully replace the infarcted myocardium with reverse LV remodeling in rats with MI.

Animals↗

PubMed2003

A pig model of chronic heart failure by intracoronary embolization with gelatin sponge.

BACKGROUND: We produced a large-animal model of left ventricular (LV) failure induced by transcatheter embolization of the left coronary artery using a gelatin sponge. METHODS: Fourteen male pigs underwent transcatheter embolization of the left anterior descending artery (LAD) using gelatin sponge to produce anteroapical myocardial infarction. Coronary angiography was performed 1 week after the coronary embolization. The animals were followed up with echocardiography and LV pressure-volume study for the subsequent 8 weeks, and the data were compared with those of the control group (n = 13). RESULTS: The procedure mortality was 2 of 14 (14%). Coronary angiography revealed the occluded LAD was recanalized with poor run-off. The LV end-diastolic dimension progressively increased (control versus myocardial infarction: 39 +/- 2 mm versus 49 +/- 4 mm, p < 0.001 at week 4; and 40 +/- 2 mm versus 57 +/- 6 mm, p < 0.001 at week 8). Fractional area change decreased over 8 weeks (77% +/- 10% versus 43% +/- 6%, p < 0.001 at week 4; and 77% +/- 10% versus 40% +/- 8%, p < 0.001 at week 8). End-systolic elastance progressively decreased over 8 weeks (3.04 +/- 0.73 mm Hg/mL versus 1.54 +/- 0.51 mm Hg/mL, p < 0.0001 at week 4; and 2.88 +/- 0.44 mm Hg/mL versus 1.05 +/- 0.21 mm Hg/mL, p < 0.001 at week 8). The plasma levels of brain natriuretic peptide were significantly higher in the study group (543 +/- 131 pg/mL versus 1,321 +/- 364 pg/mL, p < 0.001 at week 4; and 610 +/- 152 pg/mL versus 1,523 +/- 232 pg/mL, p < 0.001 at week 8). CONCLUSIONS: This pig model of chronic heart failure is reliable, reproducible, and amenable to investigate other surgical procedures.

Animals↗

PubMed2003

Toward surgical angiogenesis using slow-released basic fibroblast growth factor.

OBJECTIVE: Therapeutic angiogenesis using basic fibroblast growth factor (bFGF) in coronary artery disease has been documented in a number of papers. However, the effectiveness is discrepant among documents. In this study, we evaluated the distribution of bFGF in the rat heart by different administration methods, and investigated the efficacy of slow-released administration of bFGF using biodegradable hydrogel microspheres (bFGF microspheres) in a pig infarction model toward an enhanced coronary bypass surgery. METHODS: Heart failure due to myocardial infarction was induced in rats and pigs. In the rat study, free form of bFGF (central venous injection, intracoronary injection, and intramyocardial administration) and bFGF microspheres (intramyocardial administration) were given 4 weeks later. The remaining radioactivity of bFGF in the hearts was estimated 1, 24, and 72 h later. On the other hand, the pigs were randomized into two groups 4 weeks after myocardial infarction. While the control group (n=8) had gelatin hydrogel microspheres with saline, the FGF group (n=8) received bFGF microspheres in the left ventricular (LV) wall. RESULTS: In the rat study, after intramyocardial administration of bFGF microspheres, more bFGF remained in the rat heart 72 h later compared with the other methods (P<0.0001). In the pig study, 4 weeks after the treatment, the FGF group had smaller LV diastolic diameter (48.7+/-5.3 vs. 56.7+/-5.2 mm, P<0.01) than the control group. LV end-systolic elastance was higher in the FGF group (2.96+/-1.2 vs. 1.06+/-0.3 mmHg/ml, P<0.01). In microscopic examinations, many neovessels were found in and around the scar tissue, and the vascular density in the FGF group was significantly higher (61.5+/-18.3 vs. 153.0+/-29.0/mm2, P<0.01). In addition, the infarcted LV walls were less expanded and more thickened in the FGF group. CONCLUSIONS: Biodegradable hydrogel microspheres with bFGF improved LV function and inhibited LV remodeling by angiogenesis in pigs with chronic myocardial infarction. bFGF microspheres into ischemic myocardium may revascularize small ungraftable vessels and may potentially increase distal run-off when applied in coronary bypass surgery.

Animals↗

PubMed2002

Combined procedure of surgical repair and cell transplantation for left ventricular aneurysm: an experimental study.

BACKGROUND: This study was designed to investigate the efficacy of the combined procedure of left ventricular (LV) repair and fetal cardiomyocyte transplantation (CM-TX) in a rat myocardial infarction model. METHODS AND RESULTS: A moderate-sized LV aneurysm was created by proximal ligation of the left coronary artery in 47 Lewis rats. Four weeks later, they were underwent another operation and received culture medium injection (n=10; group I), fetal CM-TX (n=10; group II), purse-string LV repair with culture medium injection (n=14; group III), or LV repair with fetal CM-TX (n=13; group IV). They were echocardiographically followed-up during the subsequent 4 weeks, and cardiac catheterization was performed in the final week. In the late period, LV dimension in group IV was smaller than that in group III (end-diastolic dimension, 0.92+/-0.02 versus 1.01+/-0.03 cm, P=0.0090; end-systolic dimension, 0.62+/-0.02 versus 0.74+/-0.04 cm, P=0.0093; at the fourth week), although they initially showed similar decreases in both groups. At the final week, end-systolic elastance was higher in group IV than in groups I, II, or III (0.61+/-0.10 versus 0.19+/-0.03, 0.30+/-0.09, 0.33+/-0.07 mm Hg/ micro L, P=0.0002, 0.0037, and 0.0042, respectively). CONCLUSIONS: Fetal CM-TX exerted preventive effects against late LV dilation and dysfunction after LV repair in the rat model. The results suggest that repair surgery combined with fetal CM-TX may enhance the surgical benefits for patients with LV aneurysm in the long term.

Animals↗

PubMed2002

Cardiomyocyte transplantation does not reverse cardiac remodeling in rats with chronic myocardial infarction.

BACKGROUND: Several reports have documented the potential benefits of cell transplantation as an alternative to cardiac transplantation. This study was designed to investigate whether cardiomyocyte transplantation is effective in rats with chronic myocardial infarction. METHODS: Syngeneic Lewis rats were used in this study. Chronic myocardial infarction was induced in rats by ligating the left anterior descending artery. Four weeks later, after left ventricular (LV) dysfunction with akinetic regions was confirmed by echocardiography, the rats were randomized into two groups: a group that received fetal cardiomyocyte transplantation (TX group; n = 11); and a group that received an intramyocardial injection of culture medium only (control group; n = 12). RESULTS: Four weeks after treatment, the TX group had smaller end-systolic dimension (LVDs) (7.5 +/- 0.9 vs 8.9 +/- 0.8 mm, p < 0.01) and better fractional shortening (FS) (26.2 +/- 5.9 vs 17.7% +/- 5.1%, p < 0.01) than the control group. However, there were no differences in LV end-diastolic dimension, LVDs, and FS between baseline and post-treatment values in the TX group. In addition, plasma levels of atrial natriuretic peptide were not significantly different between the two groups 4 weeks after treatment. In microscopic examination, small amounts of transplanted cardiomyocytes were found only in the periinfarct area, not in the center of scar area, and a thicker ventricular wall in the infarct area was detected in the TX group. CONCLUSIONS: Fetal cardiomyocyte transplantation prevented, but did not reverse, cardiac remodeling that was accompanied with heart failure in myocardial infarction rats. Further investigation is warranted for optimal clinical application to the failing heart.

Animals↗

PubMed2002

Prevascularization with gelatin microspheres containing basic fibroblast growth factor enhances the benefits of cardiomyocyte transplantation.

OBJECTIVE: The effects of cell transplantation on the ischemic failing heart have already been documented. However, the area in and around infarct regions is not a good environment for cells to survive in because they are exposed to poor conditions in which certain requirements cannot be adequately supplied. We therefore designed a study to investigate the efficacy of prevascularization in ischemic regions before cell transplantation. METHODS: Rats with myocardial infarction were randomized into 4 groups: 11 rats received a culture medium injection to the left ventricular wall (control group), 11 received fetal cardiomyocyte transplantation (TX group), 11 received gelatin hydrogel microspheres incorporating basic fibroblast growth factor (FGF group), and 11 received basic fibroblast growth factor pretreatment sequentially, followed by cardiomyocyte transplantation (FGF-TX group). Four weeks later, left ventricular function was assessed by means of echocardiography and cardiac catheterization. RESULTS: In the FGF and FGF-TX groups neovascularization was found in the scar tissue 1 week later. The TX, FGF, and FGF-TX groups showed better fractional shortening than the control group (TX, FGF, FGF-TX, and control: 28% +/- 4.4%, 24% +/- 8.6%, 27% +/- 7.3%, and 17% +/- 4.6%, respectively; P <.01). Left ventricular maximum time-varying elastance was higher in the FGF-TX group than in the TX and FGF groups (FGF-TX, TX, and FGF: 0.52 +/- 0.23, 0.30 +/- 0.08, and 0.27 +/- 0.20 mm Hg/microL, respectively; P <.01). Histologically, more transplanted cells survived in the FGF-TX group than in the TX group. CONCLUSIONS: Prevascularization with basic fibroblast growth factor-incorporated microspheres enhances the benefits of cardiomyocyte transplantation. We expect that this system will contribute to regeneration medicine through its extensive application to other growth factors.

Animals↗