Lessons from human coronary aspirate

Kleinbongard, Petra; Konorza, Thomas; Böse, Dirk; Baars, Theodor; Haude, Michael; Erbel, Raimund; Heusch, Gerd

doi:10.1016/j.yjmcc.2011.06.022

Cited by 32 publications

(33 citation statements)

References 70 publications

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“…The aspirate retrieved during stent implantation under protection with a distal occlusion/aspiration device might serve as a biological offprint of the culprit lesion (19). We have therefore now compared intravascular ultrasound (IVUS) imaging before with quantification of the released particulate debris after stent implantation, including its calcium content, as well as determined soluble vasoconstrictors (catecholamines, endothelin, serotonin, thromboxane, and tissue factor) and an inflammatory mediator [TNF␣ as a prototype of inflammatory cytokines (11,18)] in the aspirate from stented native right coronary arteries (nRCA) versus that from SVGs on right coronary arteries (SVG-RCA).…”

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confidence: 99%

Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

Kleinbongard

Baars

Möhlenkamp

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Kleinbongard P, Baars T, Möhlenkamp S, Kahlert P, Erbel R, Heusch G. Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris. Am J Physiol Heart Circ Physiol 305: H1222-H1229, 2013. First published August 9, 2013; doi:10.1152/ajpheart.00358.2013.-Stent implantation into atherosclerotic coronary arteries releases particulate debris and soluble substances that contribute to impaired microvascular perfusion. Here we addressed the potential for microvascular obstruction in patients with stenotic native right coronary arteries (nRCA) compared with saphenous vein grafts on right coronary arteries (SVG-RCA). We enrolled symptomatic, male patients with stable angina pectoris and a flow-limiting stenosis in their nRCA or SVG-RCA (n ϭ 18/18). Plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation under protection with a distal occlusion/aspiration device and divided into particulate debris and plasma. The release of catecholamines, endothelin, serotonin, thromboxane B2, and tumor necrosis factor-␣ was measured. The response of rat mesenteric arteries with intact (ϩE) and denuded (ϪE) endothelium to aspirate plasma (without and with selective endothelin receptor blockade) was normalized to that by potassium chloride (KClmax ϭ 100%). Plaque volume and composition were not different between nRCA and SVG-RCA. There was less particulate debris (65 Ϯ 8 vs. 146 Ϯ 23 mg; P Ͻ 0.05) and more endothelin release (5.8 Ϯ 0.8 vs. 1.3 Ϯ 0.7 pg/ml; P Ͻ 0.05) in nRCA than in SVG-RCA, whereas the release of the other mediators was not different. Aspirate from nRCA induced stronger vasoconstriction than that from SVG-RCA [nRCA, 78 Ϯ 6% (ϩE)/84 Ϯ 5% (ϪE); SVG-RCA, 59 Ϯ 6% (ϩE)/68 Ϯ 3% (ϪE); P Ͻ 0.05 nRCA vs. SVG-RCA], which was attenuated by a nonspecific endothelin and a specific endothelin receptor A antagonist. Thus coronary aspirate from stented nRCA is characterized by less debris but more endothelin and stronger vasoconstrictor response than that from SVG-RCA. coronary disease; ischemia; native coronary artery; saphenous vein graft; vasoconstriction INTERVENTIONAL PLAQUE RUPTURE induces the release of not only particulate debris but also soluble vasoconstrictor, thrombogenic, and inflammatory substances from the lesion that all contribute to impair microvascular coronary perfusion. Typical consequences of coronary microvascular obstruction are microinfarcts with subsequent inflammation, arrhythmias, contractile dysfunction, and impaired coronary flow reserve (14). Various protection devices have been used to capture and remove the released plaque material. A prognostic benefit from distal protection devices in elective interventions has been established only for saphenous vein grafts (SVGs) (3, 39), whereas a benefit for native coronary arteries still remains to be demonstrated (14).The underlying atherosclerosis in native coronary arteries differs from that in SVGs,...

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confidence: 99%

Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

Kleinbongard

Baars

Möhlenkamp

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…Microembolisation refers to embolised debris with a diameter below 100 μ m. Platelet-platelets aggregates, neutrophils-platelets aggregates, monocytes-platelets aggregates [13], microthrombi [14], amorphous material [15], microparticles [16], cholesterol crystals [17], and leukocytes contribute to microemboli composition [18]. Most of the embolised material is classified as microembolisation [19].…”

Section: Distal Embolisation Definition and Pathophysiologymentioning

confidence: 99%

“…Most of the embolised material is classified as microembolisation [19]. Its consequences extend beyond its merely mechanical occluding effect as the embolic material has thrombogenic, vasoconstrictor, and inflammatory activity [15]. This pharmacological effect is also related to the occurrence of a humoral embolisation, since atherosclerotic plaques, especially if unstable and even ruptured or eroded, are rich in soluble factors able to cause or to worsen the microvascular damage during DE [20–23].…”

Section: Distal Embolisation Definition and Pathophysiologymentioning

confidence: 99%

Spontaneous and Procedural Plaque Embolisation in Native Coronary Arteries: Pathophysiology, Diagnosis, and Prevention

et al. 2013

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The detachment of atherothrombotic material from the atherosclerotic coronary plaque and downstream embolisation is an underrecognized phenomenon and it causes different degrees of impairment of the coronary microcirculation. During treatment of obstructive atherosclerotic plaque by percutaneous coronary intervention (PCI) distal embolisation (DE) is considered to be inevitable and it is associated with potential clinical and prognostic implications. This review aims to assess the main aspects of both spontaneous and procedural DE, analyze their different pathophysiology, provide specific insights on the main diagnostic tools for their identification, and finally focus on the main strategies for their treatment and prevention.

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“…Circulating 5‐HT was elevated in patients with hypertension, PAH,9, 10 coronary and peripheral artery disease and was positively correlated with intima‐media thickness of the carotid arteries 11, 12, 13, 14, 15, 16. Plasma level of 5‐HT in coronary circulation was locally increased after angioplasty, and the release of 5‐HT was thought to be from the activated platelets 17, 18…”

Section: Introductionmentioning

confidence: 99%

Inhibition of 5‐Hydroxytryptamine Receptor 2B Reduced Vascular Restenosis and Mitigated the β‐Arrestin2–Mammalian Target of Rapamycin/p70S6K Pathway

Liu

Wang

et al. 2018

JAHA

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BackgroundAs a monoamine neurotransmitter, 5‐hydroxytryptamine (5‐HT) or serotonin modulates mood, appetite, and sleep. Besides, 5‐HT also has important peripheral functions. 5‐HT receptor 2B (5‐HT2BR) plays a key role in cardiovascular diseases, such as pulmonary arterial hypertension and cardiac valve disease. Percutaneous intervention has been used to restore blood flow in occlusive vascular disease. However, restenosis remains a significant problem. Herein, we investigated the role of 5‐HT2BR in neointimal hyperplasia, a key pathological process in restenosis.Methods and ResultsThe expression of 5‐HT2BR was upregulated in wire‐injured mouse femoral arteries. In addition, BW723C86, a selective 5‐HT2BR agonist, promoted the injury response during restenosis. 5‐HT and BW723C86 stimulated migration and proliferation of rat aortic smooth muscle cells. Conversely, LY272015, a selective antagonist, attenuated the 5‐HT–induced smooth muscle cell migration and proliferation. In vitro study showed that the promigratory effects of 5‐HT2BR were mediated through the activation of mammalian target of rapamycin (mTOR)/p70S6K signaling in a β‐arrestin2–dependent manner. Inhibition of mammalian target of rapamycin or p70S6K mitigated 5‐HT2BR–mediated smooth muscle cell migration. Mice with deficiency of 5‐HT2BR showed significantly reduced neointimal formation in wire‐injured arteries.ConclusionsThese results demonstrated that activation of 5‐HT2BR and β‐arrestin2–biased downstream signaling are key pathological processes in neointimal formation, and 5‐HT2BR may be a potential target for the therapeutic intervention of vascular restenosis.

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Lessons from human coronary aspirate

Cited by 32 publications

References 70 publications

Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

Spontaneous and Procedural Plaque Embolisation in Native Coronary Arteries: Pathophysiology, Diagnosis, and Prevention

Inhibition of 5‐Hydroxytryptamine Receptor 2B Reduced Vascular Restenosis and Mitigated the β‐Arrestin2–Mammalian Target of Rapamycin/p70S6K Pathway

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