Macrophage p53 controls macrophage death in atherosclerotic lesions of apolipoprotein E deficient mice

Boesten, Lianne S.M.; Zadelaar, A. Susanne M.; Nieuwkoop, Anita van; Hu, Lihui; Teunisse, Amina F.A.S.; Jochemsen, Aart G.; Evers, Bastiaan; Water, Bob van de; Gijbels, Marion J.J.; Vlijmen, Bart J.M. van; Havekes, Louis M.; Winther, Menno P.J. de

doi:10.1016/j.atherosclerosis.2009.06.015

Cited by 34 publications

(25 citation statements)

References 28 publications

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“…On the other hand, the increased apoptosis of foam cells induced by the disruption of EP4 (the PGE2 receptor) reduces the size of early atherogenic lesions 7 . These observations support the concept that the accelerated apoptosis of foam cells could lead to reduced lesion size and a subsequent attenuation of plaque progression 5,[7][8][9][10][11] .…”

supporting

confidence: 72%

MafB promotes atherosclerosis by inhibiting foam-cell apoptosis

et al. 2014

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supporting

confidence: 72%

MafB promotes atherosclerosis by inhibiting foam-cell apoptosis

et al. 2014

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“…Necrotic macrophages accumulate in the necrotic core while losing their cell-type specific epitopes, hindering their detection. These findings are in line with previous observations in mice lacking the proapoptotic protein Bax [21], the death receptors TNFR1 [17] and Fas [20], or the tumor suppressor proteins p53 [22–26] and p19(ARF) [27]. Macrophage specific deletion of Bax reduces macrophage apoptosis and stimulates the development of advanced atherosclerotic plaques in LDL receptor knockout mice [21].…”

Section: Discussionsupporting

confidence: 90%

Caspase‐3 Deletion Promotes Necrosis in Atherosclerotic Plaques of ApoE Knockout Mice

Grootaert

Schrijvers

Hermans

et al. 2016

Oxidative Medicine and Cellular Longevity

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Apoptosis of macrophages and vascular smooth muscle cells (VSMCs) in advanced atherosclerotic plaques contributes to plaque progression and instability. Caspase-3, a key executioner protease in the apoptotic pathway, has been identified in human and mouse atherosclerotic plaques but its role in atherogenesis is not fully explored. We therefore investigated the impact of caspase-3 deletion on atherosclerosis by crossbreeding caspase-3 knockout (Casp3−/−) mice with apolipoprotein E knockout (ApoE−/−) mice. Bone marrow-derived macrophages and VSMCs isolated from Casp3−/−ApoE−/− mice were resistant to apoptosis but showed increased susceptibility to necrosis. However, caspase-3 deficiency did not sensitize cells to undergo RIP1-dependent necroptosis. To study the effect on atherosclerotic plaque development, Casp3+/+ApoE−/− and Casp3−/−ApoE−/− mice were fed a western-type diet for 16 weeks. Though total plasma cholesterol, triglycerides, and LDL cholesterol levels were not altered, both the plaque size and percentage necrosis were significantly increased in the aortic root of Casp3−/−ApoE−/− mice as compared to Casp3+/+ApoE−/− mice. Macrophage content was significantly decreased in plaques of Casp3−/−ApoE−/− mice as compared to controls, while collagen content and VSMC content were not changed. To conclude, deletion of caspase-3 promotes plaque growth and plaque necrosis in ApoE−/− mice, indicating that this antiapoptotic strategy is unfavorable to improve atherosclerotic plaque stability.

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“…28,29 Interestingly, p53-null mice are prone to enhanced atherosclerosis, 30 attributed to p53's classical roles such as apoptosis and cell cycle arrest. [31][32][33][34][35] Recently a novel role of p53 in senescence was established. [36][37][38][39] It was shown that p53 suppress senescence, while inducing cell cycle arrest.…”

Section: Discussionmentioning

confidence: 99%