Liposomal Hsp90 cDNA induces neovascularization via nitric oxide in chronic ischemia

Pfosser, Achim; Thalgott, Mark; Büttner, Kerstin; Brouet, Agnès; Feron, Olivier; Boekstegers, Peter; Kupatt, Christian

doi:10.1016/j.cardiores.2004.10.019

Cited by 35 publications

(25 citation statements)

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“…Expression levels were normalized to GAPDH and displayed as fold change to the pcDNA control situation. The comparative 2-DDC t method was carried out, calculating the delta C t values for the gene of interest and the housekeeping gene and then calculating the difference between both delta C t values 44 .…”

Section: Methodsmentioning

confidence: 99%

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MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2

et al. 2014

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Gradual occlusion of coronary arteries may result in reversible loss of cardiomyocyte function (hibernating myocardium), which is amenable to therapeutic neovascularization. The role of myocardin-related transcription factors (MRTFs) co-activating serum response factor (SRF) in this process is largely unknown. Here we show that forced MRTF-A expression induces CCN1 and CCN2 to promote capillary proliferation and pericyte recruitment, respectively. We demonstrate that, upon G-actin binding, thymosin 4 (T 4), induces MRTF translocation to the nucleus, SRF-activation and CCN1/2 transcription. In a murine ischaemic hindlimb model, MRTF-A or T 4 promotes neovascularization, whereas loss of MRTF-A/B or CCN1-function abrogates the T 4 effect. We further show that, in ischaemic rabbit hindlimbs, MRTF-A as well as T 4 induce functional neovascularization, and that this process is inhibited by angiopoietin-2, which antagonizes pericyte recruitment. Moreover, MRTF-A improves contractile function of chronic hibernating myocardium of pigs to a level comparable to that of transgenic pigs overexpressing T 4 (T 4tg). We conclude that MRTF-A promotes microvessel growth (via CCN1) and maturation (via CCN2), thereby enabling functional improvement of ischaemic muscle tissue.

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Section: Methodsmentioning

confidence: 99%

“…In female rabbits, 2-2.5 kg body weight, on day 0 the complete femoral artery of the right leg was excised 44 and rAAV application (5 Â 10 12 virus particles) was performed via i.m. injection into the right limb as indicated.…”

Section: Methodsmentioning

confidence: 99%

MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2

et al. 2014

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“…This highly conserved family of proteins function as molecular chaperones, and HSPs are involved in multiple cellular activities, including angiogenesis signaling (58,67,71). For instance, members of the HSP70 and HSP90 families have been reported to modulate angiogenesis in skeletal muscle (58,67). Pharmacological blockade of HSP70s impairs endothelial cell migration and tube formation in vitro and abrogates capillary growth in a model of peripheral arterial insufficiency (67).…”

Section: Heat Shock Proteins and Angiogenesismentioning

confidence: 99%

Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle

Kuhlenhoelter

Kim

Neff

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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Heat therapy has been shown to promote capillary growth in skeletal muscle and in the heart in several animal models, but the effects of this therapy on angiogenic signaling in humans are unknown. We evaluated the acute effect of lower body heating (LBH) and unilateral thigh heating (TH) on the expression of angiogenic regulators and heat shock proteins (HSPs) in healthy young individuals. Exposure to LBH ( n = 18) increased core temperature (Tc) from 36.9 ± 0.1 to 37.4 ± 0.1°C ( P < 0.01) and average leg skin temperature (Tleg) from 33.1 ± 0.1 to 39.6 ± 0.1°C ( P < 0.01), but did not alter the levels of circulating angiogenic cytokines and bone marrow-derived proangiogenic cells (CD34+CD133+). In skeletal muscle, the change in mRNA expression from baseline of vascular endothelial growth factor (VEGF), angiopoietin 2 (ANGPT2), chemokines CCL2 and CX3CL1, platelet factor-4 (PF4), and several members of the HSP family was higher 30 min after the intervention in the individuals exposed to LBH ( n = 11) compared with the control group ( n = 12). LBH also reduced the expression of transcription factor FOXO1 ( P = 0.03). Exposure to TH ( n = 14) increased Tleg from 32.8 ± 0.2 to 40.3 ± 0.1°C ( P < 0.05) but Tc remained unaltered (36.8 ± 0.1°C at baseline and 36.9 ± 0.1°C at 90 min). This intervention upregulated the expression of VEGF, ANGPT1, ANGPT2, CCL2, and HSPs in skeletal muscle but did not affect the levels of CX3CL1, FOXO-1, and PF4. These findings suggest that both LBH and TH increase the expression of factors associated with capillary growth in human skeletal muscle.

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“…Capillaries and myofibers were counted in 10 microscopic fields (ϫ40 magnification), and capillary density was expressed as capillary-tomyofiber ratio (36).…”

Section: Experimental Protocol the Medical College Of Wisconsin (Mcw)mentioning

confidence: 99%

Role of endothelial cell apoptosis in regulation of skeletal muscle angiogenesis during high and low salt intake

Resende

Amaral

Munzenmaier

et al. 2006

Physiological Genomics

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. Role of endothelial cell apoptosis in regulation of skeletal muscle angiogenesis during high and low salt intake. Physiol Genomics 25: 325-335, 2006. First published February 7, 2006 doi:10.1152/physiolgenomics.00253.2005.-Angiogenesis, under normal conditions, is a tightly regulated balance between pro-and antiangiogenic factors. The goal of this study was to investigate the mechanisms involved in the control of the skeletal muscle angiogenic response induced by electrical stimulation during the suppression of plasma renin activity (PRA) with a high-salt diet. Rats fed 0.4% or 4% salt diets were exposed to electrical stimulation for 7 days. The tibialis anterior (TA) muscles from stimulated and unstimulated hindlimbs were removed and prepared for gene expression analysis, CD31-terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) double-staining assay, and Bcl-2 and Bax protein expression by Western blot. Rats fed a low-salt diet showed a dramatic angiogenesis response in the stimulated limb compared with the unstimulated limb. This angiogenesis response was significantly attenuated when rats were placed on a high-salt diet. Microarray analysis showed that in the stimulated limb of rats fed a low-salt diet many genes related to angiogenesis were upregulated. In contrast, in rats fed a high-salt diet most of the genes upregulated in the stimulated limb function in apoptosis and cell cycle arrest. Endothelial cell apoptosis, as analyzed by CD31-TUNEL staining, increased by fourfold in the stimulated limb compared with the unstimulated limb. There was also a 48% decrease in the Bcl-2-to-Bax ratio in stimulated compared with unstimulated limbs of rats fed a high-salt diet, confirming severe apoptosis. This study suggests that the increase in endothelial cell apoptosis in TA muscle might contribute to the attenuation of angiogenesis response observed in rats fed a high-salt diet.Bax; Bcl-2; gene expression THE GROWTH OF NEW BLOOD VESSELS plays a critical role in normal physiological processes but is also central to the progression of many diseases. Angiogenesis is involved in several disorders such as cancer, diabetic retinopathy, macular degeneration, and endometriosis (15). In an attempt to control pathological angiogenesis, a growing interest in better understanding prosurvival and prodeath signals has emerged (7,8,26,34). Each endothelial cell within a vessel wall is exposed to a combination of prosurvival and prodeath signals. The sum of these signals determines whether the cell remains viable or undergoes apoptosis (10).Our laboratory has demonstrated that physiological, pharmacological, or genetic manipulation of the renin-angiotensin system (RAS) has an important impact on both the basal number of microcirculatory blood vessels and the ability of tissues to undergo angiogenesis induced by exercise (3) or electrical stimulation (2). In previous studies (4), we demonstrated that transfer of a region of chromosome 13 containing the renin gene from Dahl R into Dahl S rats restores both p...

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Liposomal Hsp90 cDNA induces neovascularization via nitric oxide in chronic ischemia

Cited by 35 publications

References 32 publications

MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2

MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2

Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle

Role of endothelial cell apoptosis in regulation of skeletal muscle angiogenesis during high and low salt intake

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