Myocardial infarction accelerates atherosclerosis

Abstract

SUMMARY During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaque in the arterial wall and cause its 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 ischemic 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. When seeking the source of surplus monocytes in plaque, we found that myocardial infarction liberated hematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signaling. 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.

Orthopedic surgery increases atherosclerotic lesions and necrotic core area in ApoE−/− mice

“…We did not find indications of fibrous cap thinning after orthopedic surgery, which besides necrotic core expansion is another hallmark of vulnerable, inflammatory plaque 8,22 . We M A N U S C R I P T…”

“…ApoE-/-mice demonstrated that the systemic inflammatory response to myocardial infarction aggravates chronic atherosclerosis 22 . Together with the results described herein, these studies support an important role for systemic inflammation in plaque destabilization and might thereby contribute to increased risk of cardiovascular events.…”

“…In addition, other, non-or indirect inflammatory effects of surgery could be further explored. For instance, hemodynamic disturbances 27 , sympathetic nerve system activation 28 or enhanced platelet activity 29 are potential contributors to atherosclerotic lesion development and increased cardiovascular risk. Furthermore it would be interesting to test our findings in advanced mouse models to study actual plaque complications rather than atherosclerotic plaque development alone 30,31 .…”

High Levels of (Un)Switched Memory B Cells Are Associated With Better Outcome in Patients With Advanced Atherosclerotic Disease

“…The risk of cardiovascular events is particularly high in patients with earlier CVD manifestations 6, 7. For example, the 3‐year cumulative incidence of major adverse cardiovascular events in patients undergoing carotid endarterectomy was 13% 8.…”

Is Immunomodulation a Principal Mechanism Underlying How Cell-Based Therapies Enhance Stroke Recovery?

“…In parallel to events within the brain, lymphocytes, neutrophils, and monocytes traffic to the brain from the periphery and contribute to further neuronal damage. The spleen is a principal reservoir that reduces in size after stroke, releasing inflammatory cells and cytokines into the circulation [8][9][10][11][12][13][14][15]. In addition, the bone marrow mobilizes a subpopulation of multipotent stem cells into the peripheral blood following stroke, which is then directed towards the brain, as well as peripheral organs such as the spleen [16].…”