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Myocardial infarction accelerates atherosclerosis.

Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS, Iwamoto Y, Thompson B, Carlson AL, Heidt T, Majmudar MD, Lasitschka F, Etzrodt M, Waterman P, Waring MT, Chicoine AT, van der Laan AM, Niessen HW, Piek JJ, Rubin BB, Butany J, Stone JR, Katus HA, Murphy SA, Morrow DA, Sabatine MS, Vinegoni C, Moskowitz MA, Pittet MJ, Libby P, Lin CP, Swirski FK, Weissleder R, Nahrendorf M - Nature (2012)

Bottom Line: Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons.Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis.These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.

View Article: PubMed Central - PubMed

Affiliation: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.

ABSTRACT
During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.

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Elevated levels of progenitor cells in the spleen of apoE−/− mice after MIa, Quantification for HSPCs, MDPs, and GMPs at different time points after MI (n = 3–15 per group). The gating strategy is shown in Supplementary Fig. 10. b, Number of colony-forming units. Mean ± s.e.m., * P < 0.05, ** P < 0.01.
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Figure 2: Elevated levels of progenitor cells in the spleen of apoE−/− mice after MIa, Quantification for HSPCs, MDPs, and GMPs at different time points after MI (n = 3–15 per group). The gating strategy is shown in Supplementary Fig. 10. b, Number of colony-forming units. Mean ± s.e.m., * P < 0.05, ** P < 0.01.

Mentions: Because the spleen has the ability to host extramedullary hematopoiesis19–21, we measured splenic monocyte progenitor content following MI. Hematopoietic progenitor cell numbers in the spleen increased post-MI (Fig. 2, Supplementary Fig. 9) but not in the bone marrow (Supplementary Fig. 10). Proliferation of progenitors doubled in the spleen (Supplementary Fig. 11). In patients that died after an acute MI, we found increased numbers of c-kit+ cells in the spleen, some of which colocalized with the proliferation marker Ki-67 (Supplementary Fig. 12).


Myocardial infarction accelerates atherosclerosis.

Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS, Iwamoto Y, Thompson B, Carlson AL, Heidt T, Majmudar MD, Lasitschka F, Etzrodt M, Waterman P, Waring MT, Chicoine AT, van der Laan AM, Niessen HW, Piek JJ, Rubin BB, Butany J, Stone JR, Katus HA, Murphy SA, Morrow DA, Sabatine MS, Vinegoni C, Moskowitz MA, Pittet MJ, Libby P, Lin CP, Swirski FK, Weissleder R, Nahrendorf M - Nature (2012)

Elevated levels of progenitor cells in the spleen of apoE−/− mice after MIa, Quantification for HSPCs, MDPs, and GMPs at different time points after MI (n = 3–15 per group). The gating strategy is shown in Supplementary Fig. 10. b, Number of colony-forming units. Mean ± s.e.m., * P < 0.05, ** P < 0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3401326&req=5

Figure 2: Elevated levels of progenitor cells in the spleen of apoE−/− mice after MIa, Quantification for HSPCs, MDPs, and GMPs at different time points after MI (n = 3–15 per group). The gating strategy is shown in Supplementary Fig. 10. b, Number of colony-forming units. Mean ± s.e.m., * P < 0.05, ** P < 0.01.
Mentions: Because the spleen has the ability to host extramedullary hematopoiesis19–21, we measured splenic monocyte progenitor content following MI. Hematopoietic progenitor cell numbers in the spleen increased post-MI (Fig. 2, Supplementary Fig. 9) but not in the bone marrow (Supplementary Fig. 10). Proliferation of progenitors doubled in the spleen (Supplementary Fig. 11). In patients that died after an acute MI, we found increased numbers of c-kit+ cells in the spleen, some of which colocalized with the proliferation marker Ki-67 (Supplementary Fig. 12).

Bottom Line: Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons.Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis.These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.

View Article: PubMed Central - PubMed

Affiliation: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.

ABSTRACT
During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.

Show MeSH
Related in: MedlinePlus