Heart failure (HF) ensuing myocardial infarction (MI) is characterized by the initiation of a systemic inflammatory response. We aimed to elucidate the impact of myelomonocytic cells and their activation by angiotensin II on vascular endothelial function in a mouse model of HF after MI. HF was induced in male C57BL/6J mice by permanent ligation of the left anterior descending coronary artery. Compared to sham, HF mice had significantly impaired endothelial function accompanied by enhanced mobilization of Sca-1⁺c-Kit⁺ haematopoietic stem cells and Sca-1⁻c-Kit⁺ common myeloid and granulocyte-macrophage progenitors in the bone marrow as well as increased vascular infiltration of CD11b⁺Ly6G⁻Ly6C^high monocytes and accumulation of CD11b⁺ F4/80⁺ macrophages, assessed by flow cytometry. Using mice with Cre-inducible expression of diphtheria toxin receptor in myeloid cells, we selectively depleted lysozyme M⁺ myelomonocytic cells for 10 days starting 28 days after MI. While the cardiac phenotype remained unaltered until 38 days post-MI, myeloid cell depletion attenuated vascular accumulation of Nox2⁺CD45⁺ cells, endothelial dysfunction, oxidative stress, and vascular expression of adhesion molecules and angiotensin II receptor type 1 (AT1R). Pharmacological blockade of this receptor for 4 weeks did not significantly alter cardiac function, but mimicked the effects of myeloid cell depletion: telmisartan (20 mg/kg/day, fed to C57BL/6J mice) diminished bone marrow myelopoesis and myeloid reactive oxygen species production, attenuated endothelial leucocyte rolling and vascular accumulation of CD11b⁺Ly6G⁻Ly6C^high monocytes and macrophages, resulting in improved vascular function with less abundance of Nox2⁺CD45⁺ cells. Endothelial dysfunction in HF ensuing MI is mediated by inflammatory Nox2⁺ myeloid cells infiltrating the vessel wall that can be targeted by AT1R blockade.

Aims: Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a cornerstone of drug therapy after myocardial infarction (MI) and improve left ventricular function and survival. We aimed to elucidate the impact of early treatment with the ACE inhibitor ramipril on the hematopoietic response after MI, as well as on the chronic systemic and vascular inflammation. Methods and Results: In a mouse model of MI, induced by permanent ligation of the left anterior descending artery, immediate initiation of treatment with ramipril (10 mg/k/d via drinking water) reduced cardiac inflammation and the number of circulating inflammatory monocytes, whereas left ventricular function was not altered significantly, respectively. This effect was accompanied by enhanced retention of hematopoietic stem cells, Lin⁻Sca1⁻c-Kit⁺CD34⁺CD16/32⁺ granulocyte–macrophage progenitors (GMP) and Lin⁻Sca1⁻c-Kit⁺CD150⁻CD48⁻ multipotent progenitors (MPP) in the bone marrow, with an upregulation of the niche factors Angiopoetin 1 and Kitl at 7 d post MI. Long-term ACE inhibition for 28 d limited vascular inflammation, particularly the infiltration of Ly6C^high monocytes/macrophages, and reduced superoxide formation, resulting in improved endothelial function in mice with ischemic heart failure. Conclusion: ACE inhibition modulates the myeloid inflammatory response after MI due to the retention of myeloid precursor cells in their bone marrow reservoir. This results in a reduction in cardiac and vascular inflammation with improvement in survival after MI.

Background:Although many countries have introduced strict guidelines regarding mouth and nose coverage in public to contain infection rates during the SARS-CoV-2 pandemic, more information is needed regarding the impact of wearing face masks on lactate thresholds (LT) and performance parameters during exercise.Methods:Ten healthy male and 10 healthy female subjects (age = 33.4 [10.26] y, body mass index = 23.52 [2.36] kg/m²) performed 3 incremental performance tests, wearing no mask (NM), surgical mask (SM), and filtering face piece mask class 2 (FFP2), with a cycle ergometer. The authors analyzed changes in the LT, in blood gas parameters, and in the rating of perceived exertion (RPE).Results:Performance at LT remained unchanged in subjects wearing SM or FFP2 in comparison with NM (162.5 [50.6] vs 167.2 [58.9] vs 162.2 [58.4] W with NM, SM, and FFP2, respectively,P = .24). However, the peak performance was significantly reduced wearing FFP2 compared with NM (213.8 [71.3] vs 230.5 [77.27] W, FFP2 vs NM, respectively,P < .001). Capillary pCO2 was increased while wearing SM as well as FFP2 compared with NM (29 [3.1] vs 33.3 [4] vs 35.8 [4.9] mmHg with NM, SM, and FFP2, respectively;P < .001), and pO2 decreased under maximum performance (84 [6.7] vs 79.1 [7.5] vs 77.3 [8.2] mmHg with NM, SM, and FFP2,P < .01). Importantly, rating of perceived exertion was significantly increased by wearing FFP2 compared with NM at LT according to Mader (16.7 [2.7] vs 15.3 [1.8] FFP2 vs NM, respectively,P < .01).Conclusion:Wearing face masks during exercise showed no effect on LT, limited maximum performance, and induced discrete changes in capillary pCO2 and pO2 within the physiologic range while increasing RPE at LT.