Reduced microvascular density in non-ischemic myocardium of patients with recent non-ST-segment-elevation myocardial infarction
Introduction
Myocardial microcirculatory dysfunction is a strong predictor of coronary events, leading Lerman et al. [1] to propose that acute coronary syndrome presentation depends not only on the presence of vulnerable plaque but also on the vulnerable myocardium and its microcirculation. Consistent with this proposal, Uren et al. [2] reported reduced coronary vasodilator reserve and maximal blood flow not only in the infarcted myocardium but also in myocardium remote from the site of infarction at one week and six months following myocardial infarction (MI), in comparison with patients with coronary artery disease (CAD) without MI. In addition, several studies show that myocardium supplied by non-diseased coronary vessels in patients with CAD without MI has a lower vasodilator reserve and maximal blood flow than myocardium of patients without CAD [3], [4], [5]. For patients with MI, the lower blood flow of myocardium remote from the site of infarction may be a consequence of coronary microvascular dysfunction and increased left ventricular (LV) filling pressure [6], [7], but may also reflect an alternative mechanism of impaired myocardial perfusion [2], such as reduced myocardial microvascular density.
In the present study we investigated the hypothesis that patients with recent non-ST-segment-elevation MI (NSTEMI) have lower microvascular density of non-ischemic myocardium remote from the site of infarction than patients with similarly extensive CAD without previous MI. To examine the association of microvascular density with CAD per se, we also studied patients with aortic stenosis (AS) with and without CAD, and a group of patients with “normal” LV without CAD. Our finding that NSTEMI patients had reduced arteriolar and capillary length density of non-ischemic myocardium led us to also study myocardial expression of hypoxia-inducible factor-1α (HIF1α). In addition, given that the lower myocardial microvascular density of NSTEMI patients suggested decreased myocardial angiogenesis, we measured plasma levels of angiogenesis-related biomarkers in no-MI and NSTEMI patients and examined the relationship between capillary length density and angiogenesis-related biomarkers.
Section snippets
Patients
The St. Vincent's Health Human Research Ethics Committee approved this research and all patients gave written informed consent. Details of the St. Vincent's Health Cardiac Tissue Bank are described elsewhere [8]. From each patient recruited to the Tissue Bank, a partial-thickness wedge-shaped biopsy was taken during surgery, immediately after cardioplegia, from a region of the lateral wall of the LV near the base of the heart, between the territories of the left anterior descending and
Study patients
The characteristics of no-MI and NSTEMI patients are shown in Table 1. The median duration of angina before surgery for the 51 no-MI patients with angina was 6 (range 0.75–360) months; an additional six patients did not have angina and came to coronary artery surgery after medical workup for planned major non-cardiac surgery or had a strong family history of CAD. The median duration of angina for the 19 NSTEMI patients with angina before their NSTEMI was 2 (range 0.1–60) months, and an
Discussion
We found a lower microvascular density in non-ischemic myocardium of patients with recent NSTEMI than in patients with similar extent of CAD without previous MI, in association with alteration in plasma levels of angiogenesis-related biomarkers. These data provide support for the proposal that acute coronary syndrome presentation depends not only on the presence of vulnerable plaque but also on the vulnerable myocardium and its microcirculation [1], and suggest that reduced microvasculature
Conclusion
Patients with recent NSTEMI had a lower microvascular density in non-ischemic myocardium than patients with similar extent of CAD without previous MI, in association with altered plasma levels of angiogenesis-related biomarkers. In addition, we found plasma LMWF and VEGFR-1 levels were correlated with myocardial capillary length density in no-MI patients. Our data provide support for the proposal that acute coronary syndrome presentation depends not only on the presence of vulnerable plaque but
Funding sources
This work was funded by grants from the National Health and Medical Research Council of Australia and from the National Heart Foundation of Australia. D.J.C. (Grant ID 395508) and D.J.K. (Grant ID 566867) are recipients of Senior Research Fellowships from the National Health and Medical Research Council of Australia. St Vincent's Institute of Medical Research is supported in part by the Victorian Government's Operational Infrastructure Support Program.
Disclosures
None.
Acknowledgments
We thank Laura Stamp, Robyn Kelly, Kim Hewitt, and Francoise Campbell for assistance with histology.
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
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