Attenuation of Apoptosis by Telmisartan in Atherosclerotic Plaques of Apolipoprotein E^−/− Mice: Evaluation Using Technetium 99m–Annexin A5

Abstract

Technetium 99m (99mTc)-annexin A5, a marker of ongoing apoptosis, is supposed to be useful in the detection of metabolically active atheroma. The aim of this study was to determine the potential of 99mTc-annexin A5 for evaluating the therapeutic effects of an angiotensin II receptor type 1 blocker (ARB) (telmisartan) on atherosclerosis. Male apolipoprotein E-/- mice were divided into telmisartan-treated (3 mg/kg/d, n = 10) and control (n = 10) groups. After 16 to 21 weeks of treatment, 99mTc-annexin A5 was injected and cryostat sections of aortic tissues (n = 10-12/aorta) were prepared. The 99mTc-annexin A5 accumulation level in the plaques was evaluated by autoradiography. Serial sections of the plaques were histologically examined to identify the lesion phenotypes (normal vessels, early lesions, atheromatous lesions, and fibrotic lesions), plaque size, macrophage infiltration levels, and lipid deposition levels. Telmisartan treatment significantly decreased the plaque size (0.05 ± 0.05 vs 0.11 ± 0.08, mm2), macrophage infiltration level (0.02 ± 0.02 vs 0.03 ± 0.02, mm2), lipid deposition level (0.01 ± 0.01 vs 0.02 ± 0.02, mm2), and 99mTc-annexin A5 accumulation level (1.30 ± 1.09 vs 2.15 ± 1.91, × 10-6/g). 99mTc-annexin A5 accumulation levels in the plaques positively correlated with macrophage infiltration (r = .69, p < .05) and lipid deposition (r = .66, p < .05) levels. Apoptosis imaging with 99mTc-annexin A5 may be useful for evaluating the therapeutic effects of ARBs on atherosclerosis.

High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma A-FABP and cholesterol: a pilot study of high fat diet and its intervention with Lactobacillus rhamnosus GG (LGG) or telmisartan in ApoE−/− mice

“…1). While TLM is used as a control to reduce atherosclerotic plaque size in ApoE −/− mice [35–37], certain probiotics including L. acidophilus ATCC 4358 [18] and Enterococcus faecium CRL183 & L. helveticus 416 [17] had been previously shown to reduce atherosclerotic plaque size in ApoE −/− mice and rabbits on hypercholesterolemic diet respectively. Such reduction might be modulated through lowering oxidative stress and inflammation [18].…”

“…Clinically, TLM is used to treat hypertension, including patients with atherosclerosis [32], and can improve endothelial [33] and cardiovascular [34] functions. In vivo, it was proven to relieve atherosclerosis in the ApoE −/− mice [35–37], and had recently been documented to reduce colonic inflammation in rats with inflammatory bowel disease [38]. We examined the effects of LGG and TLM supplementation in HF diet in terms of several atherosclerosis parameters and colonic gut microbiota, and identified some potentially important gut microbes in the pathogenesis of atherosclerosis.…”

Recent Advances in the Development of PET/SPECT Probes for Atherosclerosis Imaging

“…Hartung et al [65] evaluated the potentials of 99m Tc-annexin A5 to monitor the effects of simvastatin treatment in a rabbit model. We also used 99m Tc-annexin A5 to monitor the effects of ARBs, telmisartan, and irbesartan in a mouse model [63,66]. ARB treatment significantly decreased the plaque size, macrophage infiltration level, lipid deposition level, apoptotic cell number, and 99m Tc-annexin A5 accumulation level.…”

Multimodality Molecular Imaging of Cardiovascular Disease Based on Nanoprobes

“…Several research groups have successfully imaged cell apoptosis in atherosclerotic plaques in vivo [65][66][67]. Van Tilborg et al developed and applied a small micellar fluorescent annexin A5-functionalized nanoprobe, which carried multiple Gd-labeled lipids and fluorescent lipids for both noninvasive MRI and fluorescence imaging [68].…”