暂无摘要。

BACKGROUND: Myocardial bridging (MB) is accompanied by the dynamic extravascular compression of epicardial coronary arteries, leading to intracoronary hemodynamic disturbance with abnormal coronary flow profiles. We aimed to evaluate the prognostic implications of resistive reserve ratio (RRR), a composite measure of flow and pressure parameters that represents the vasodilatory capacity of the coronary arteries, in patients with angina with nonobstructive coronary artery disease (ANOCA) and MB, in comparison with coronary flow reserve (CFR).
RESULTS: In this retrospective cohort study, we included patients with ANOCA who underwent coronary reactivity testing, where MB was identified by transient constriction in coronary artery segments between systole and diastole. Abnormal CFR and RRR were defined as <2.5 and <2.62, respectively. Major adverse cardiac events, including cardiovascular death, stroke, myocardial infarction, heart failure, and late revascularization, served as outcomes. Among 1251 patients with ANOCA, 191 (15.3%) had MB. The prevalence of abnormal CFR or RRR was not significantly different between patients with and without MB (P=0.144 and P=0.398, respectively). Over a median follow-up time of 6.9 years, abnormal RRR predicted major adverse cardiac events in patients with MB (hazard ratio [HR], 4.38 [95% CI, 1.71-11.21]; P=0.002) and without MB (HR, 1.91 [95% CI, 1.38-2.64]; P<0.001). Abnormal CFR predicted major adverse cardiac events in patients without MB (HR, 2.15 [95% CI, 1.54-3.00]; P<0.001), whereas it was not predictive of major adverse cardiac events in patients with MB (HR, 2.29 [95% CI, 0.93-5.65]; P=0.073).
CONCLUSIONS: In patients with ANOCA and MB, impaired RRR was superior to impaired CFR in distinguishing patients at a higher risk of future adverse events, suggesting that RRR may serve as a risk stratification tool in patients with MB and ANOCA.

UNASSIGNED: Geometrical alterations in the coronary resistance artery network and the potential involvement of Tenascin C (TNC) extracellular matrix protein were investigated in diabetic and control mice.
UNASSIGNED: Diabetes was induced by streptozotocin (STZ) injections (n = 7-11 animals in each group) in Tenascin C KO (TNC KO) mice and their Wild type (A/J) littermates. After 16-18 weeks the heart was removed and the whole subsurface network of the left coronary artery was prepared (down to branches of 40 μ m outer diameter), in situ pressure-perfused and studied using video-microscopy. Outer and inner diameters, wall thicknesses and bifurcation angles were measured on whole network pictures reconstructed into collages at 1.7 μ m pixel resolutions.
UNASSIGNED: Diabetes induced abnormal morphological alterations including trifurcations, sharp bends of larger branches, and branches directed retrogradely (p < 0.001 by the χ 2 test). Networks of TNC KO mice tended to form early divisions producing parallelly running larger branches (p < 0.001 by the χ 2 probe). Networks of coronary resistance arteries were substantially more abundant in 100-180 μ m components, appearing in 2-5 mm flow distance from orifice in diabetes. This was accompanied by thickening of the wall of larger arterioles ( > 220 μ m) and thinning of the wall of smaller (100-140 μ m) arterioles (p < 0.001). Blood flow should cover larger distances in diabetic networks, but interestingly STZ-induced diabetes did not generate further geometrical changes in TNC KO mice.
UNASSIGNED: Diabetes promotes hypertrophic and hypotrophic vascular remodeling and induces vasculogenesis at well defined, specific positions of the coronary vasculature. TNC plays a pivotal role in the formation of coronary network geometry, and TNC deletion causes parallel fragmentation preventing diabetes-induced abnormal vascular morphologies.

Ischemic heart disease is currently the most common cause of mortality and morbidity worldwide. Although myocardial ischemia is classically determined by epicardial coronary atherosclerosis, up to 40% of patients referred for coronary angiography have no obstructive coronary artery disease (CAD). Ischemia with non-obstructive coronary artery disease (INOCA) has typically been underestimated in the past because, until recently, its prognostic significance was not completely clear. This review aims to highlight differences and patterns in myocardial ischemia caused by epicardial obstructive CAD, coronary microvascular dysfunction (CMD) or vasomotor abnormalities and to elucidate the state of the art in correctly diagnosing these different patterns.

Coronary microvascular dysfunction (CMD) plays a crucial role across the spectrum of heart failure (HF) pathology, contributing to disease development, progression, and outcomes. The pathophysiological mechanisms linking CMD to HF are complex and still not completely understood and include chronic inflammation, oxidative stress, and neurohormonal activation. Despite the diagnostic and prognostic relevance in patients with HF, there is no specific therapeutic strategy targeting CMD to date. Moreover, the diagnosis of this clinical condition is challenging. In this review article, we aim to discuss the different clinical pathogenetic mechanisms linking CMD to HF across the different spectra of these diseases, their prognostic relevance, and the possible therapeutic targets along with the remaining knowledge gaps in the field.

UNASSIGNED: Patients with spinal cord injuries (SCIs) are at a greater risk for the development of cardiovascular diseases (CVDs) than able-bodied individuals due to the high risk of endothelial dysfunction.
UNASSIGNED: For instance, patients with SCIs lose autonomic control of the heart and vasculature, which results in severe fluctuations in blood pressure. These oscillations between hypotension and hypertension have been shown to damage blood vessel endothelial cells and may contribute to the development of atherosclerosis. Furthermore, the loss of skeletal muscle control results in skeletal muscle atrophy and inward remodeling of the conduit arteries. It has been shown that blood vessels in the legs are chronically exposed to high shear, while the aorta experiences chronically low shear. These alterations to shear forces may adversely impact endothelial vasodilatory capacity and promote inflammatory signaling and leukocyte adherence. Additionally, microvascular endothelial vasodilatory capacity is impaired in patients with an SCI, and this may precede changes in conduit artery endothelial function. Finally, due to immobility and a loss of skeletal muscle mass, patients with SCIs have a higher risk of metabolic disorders, inflammation, and oxidative stress.
UNASSIGNED: Collectively, these factors may impair endothelium-dependent vasodilatory capacity, promote leukocyte adhesion and infiltration, promote the peroxidation of lipids, and ultimately support the development of atherosclerosis. Therefore, future interventions to prevent CVDs in patients with SCIs should focus on the management of endothelial health to prevent endothelial dysfunction and atherosclerosis.

UNASSIGNED: Diabetic retinopathy (DR) is a major microvascular complication of type 2 diabetes mellitus (T2DM). Myelomonocytic proangiogenic cells (PAC) have been implicated in DR pathogenesis, but their functional and developmental abnormalities are unclear. In this study we assessed PAC characteristics from healthy controls, T2DM patients with DR (DR) and without (NoDR) in order to determine the consequence of the diabetic condition on PAC phenotype and function, and whether these differ between DR and NoDR patients.
UNASSIGNED: PAC were generated by culturing PBMC on fibronectin coating and then immunophenotyped using flow cytometry. Furthermore, cells were sorted based on CD14, CD105, and CD133 expression and added to an in vitro 3-D endothelial tubule formation assay, containing GFP-expressing human retinal endothelial cells (REC), pericytes, and pro-angiogenic growth factors. Tubule formation was quantified by fluorescence microscopy and image analysis. Moreover, sorted populations were analyzed for angiogenic mediator production using a multiplex assay.
UNASSIGNED: The expression of CD16, CD105 and CD31, but not CD133, was lower in PAC from T2DM patients with or without DR. Myeloid and non-myeloid T2DM-derived sorted populations increased REC angiogenesis in vitro as compared to control cultures. They also showed increased S100A8 secretion, decreased VEGF-A secretion, and similar levels of IL-8, HGF, and IL-3 as compared to healthy control (HC)-derived cell populations.
UNASSIGNED: T2DM PAC are phenotypically and functionally altered compared to PAC from HC. Differences between DR and NoDR PAC are limited. We propose that impaired T2DM PAC provide inadequate vascular support and promote compensatory, albeit pathological, retinal neovascularization.

BACKGROUND: Patients with myocardial ischemia without obstructive coronary artery disease often have coronary microvascular dysfunction (CMD) and associated increased risk of cardiovascular (CV) events and anginal hospitalizations. Epicardial adipose tissue (EAT) covers much of the myocardium and coronary arteries and when dysfunctional, secretes proinflammatory cytokines and is associated with CV events. While oxidative stress and systemic inflammation are associated with CMD, the relationship between EAT and CMD in women is not well known.
METHODS: Women diagnosed with CMD (n = 21) who underwent coronary computed tomography with coronary artery calcium (CAC) scoring were compared to a reference group (RG) of women referred for CAC screening for preventive risk assessment (n = 181). EAT attenuation (Hounsfield units (HU)) was measured adjacent to the proximal right coronary artery, along with subcutaneous adipose tissue (SCAT). Two-sample t-tests with unequal variances were utilized.
RESULTS: Mean age of the CMD group was 56 ± 8 years and body mass index (BMI) was 31.6 ± 6.8 kg/m2. CV risk factors in the CMD group were prevalent: 67 % hypertension, 44 % hyperlipidemia, and 33 % diabetes. Both CMD and RG had similar CAC score (25.86 ± 59.54 vs. 24.17 ± 104.6; p = 0.21. In the CMD group, 67 % had a CAC of 0. Minimal atherosclerosis (CAD-RADS 1) was present in 76 % of women with CMD. The CMD group had lower EAT attenuation than RG (-103.3 ± 6.33 HU vs. -97.9 ± 8.3 HU, p = 0.009, respectively). There were no differences in SCAT attenuation. Hypertension, smoking history, age, BMI, and CAC score did not correlate with EAT in either of the groups.
CONCLUSIONS: Women with CMD have decreased EAT attenuation compared to RG women. EAT-mediated inflammation and changes in vascular tone may be a mechanistic contributor to abnormal microvascular reactivity. Clinical trials testing therapeutic strategies to decrease EAT may be warranted in the management of CMD.

Myocardial ischemia is a complex condition which may result from epicardial and/or microvascular causes involving functional and structural mechanisms. These mechanisms may overlap in a given patient illustrating the difficulties for appropriate management. Assessment of myocardial ischemia can be performed using noninvasive and invasive tools. However, despite living in the era of individualized precision medicine, these tools are not yet used in a broader fashion. Emerging noninvasive techniques such as quantitative perfusion cardiac magnetic resonance imaging (CMR) and stress perfusion computed tomography (CT) or photon-counting CT techniques may contribute to new standards in the assessment of stable angina patients. Invasive evaluation of myocardial ischemia should not only focus on hemodynamically relevant epicardial disease but also involve coronary vasomotor function testing (coronary spasm, coronary flow reserve, and microvascular resistance) where appropriate. Optimal patient management will depend on accurate and comprehensive diagnostic evaluation of myocardial ischemia and development of new treatment options in the future.

Microvascular dysfunction following myocardial infarction exacerbates coronary flow obstruction and impairs the preservation of ventricular function. The apelinergic system, known for its pleiotropic effects on improving vascular function and repairing ischemic myocardium, has emerged as a promising therapeutic target for myocardial infarction. Despite its potential, the natural apelin peptide has an extremely short circulating half-life. Current apelin analogs have limited receptor binding efficacy and poor targeting, which restricts their clinical applications. In this study, we utilized an enzyme-responsive peptide self-assembly technique to develop an enzyme-responsive small molecule peptide that adapts to the expression levels of matrix metalloproteinases in myocardial infarction lesions. This peptide is engineered to respond to the high concentration of matrix metalloproteinases in the lesion area, allowing for precise and abundant presentation of the apelin motif. The changes in hydrophobicity allow the apelin motif to self-assemble into a supramolecular multivalent peptide ligand-SAMP. This self-assembly behavior not only prolongs the residence time of apelin in the myocardial infarction lesion but also enhances the receptor-ligand interaction through increased receptor binding affinity due to multivalency. Studies have demonstrated that SAMP significantly promotes angiogenesis after ischemia, reduces cardiomyocyte apoptosis, and improves cardiac function. This novel therapeutic strategy offers a new approach to restoring coronary microvascular function and improving damaged myocardium after myocardial infarction.