Role In Microvascular Function Research Articles

Coronary microvascular dysfunction in patients with Takotsubo syndrome

BackgroundThe pathophysiology of Takotsubo syndrome (TTS) remains incompletely understood. While coronary microvascular dysfunction (CMD) is a potential pathophysiologic mechanism, evidence is limited. ObjectivesWe sought to evaluate CMD in patients with TTS. MethodsConsecutive patients diagnosed with TTS were included and underwent coronary angiography with invasive microvascular function evaluation, including fractional flow reserve, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR), and Resistive Reserve Ratio (RRR). Patients had an echocardiography evaluation during their index admission and at approximately 6 weeks. ResultsThirty patients were included (mean age 74 ±9, 90 % female). Twenty-five patients (83 %) had at least one abnormal coronary microvascular function parameter. Abnormal parameters included CFR<2.5 in 20 patients (67 %), IMR>25 in 18 patients (60 %), and RRR<3.5 in 25 (83 %). Longer time from symptoms to angiography correlated with a higher CFR (r = 0.51, P<0.01), and had an area under the receiver operating characteristic curve of 0.793 (95 % CI 0.60-0.98) for pathologic CFR. Patients with emotional trigger had a lower rate of pathologic IMR compared with non-emotional trigger (36 % vs 81 %, p = 0.01). Follow up echocardiography performed at a median of 1.5 months (IQR 1.15-6) showed an improvement in left ventricular ejection fraction for all patients (from mean of 40 % to 57 %). ConclusionCMD was present in most patients with TTS. The role of microvascular function in TTS may vary according to the clinical presentation and RRR may be more sensitive for the diagnosis of CMD in TTS.

Ischemia preconditioning alleviates ischemia/reperfusion injury-induced coronary no-reflow and contraction of microvascular pericytes in rats.

Ischemia preconditioning (IPC) ameliorates coronary no-reflow induced by ischemia/reperfusion (I/R) injury, and pericytes play an important role in microvascular function. However, it is unclear whether IPC exerts a protective effect on coronary microcirculation and regulates the pericytes. The purpose of this study was to assess whether IPC improves coronary microvascular perfusion and reduces pericyte constriction after myocardial I/R injury. Rats were randomly divided into three groups: the sham group, the I/R group, and the IPC+I/R group. The left anterior descending artery (LAD) of rats in the I/R group were ligated for 45min, and the rats in the IPC+I/R group received 4 episodes of 6min occlusion followed by 6min reperfusion before the LAD was ligated. After 24h of reperfusion, the area of no-reflow, and area at risk were evaluated with thioflavin-S and Evens blue staining, and infarct size with triphenyl tetrazolium chloride staining, respectively. Besides, fluorescent microspheres were perfused to enable visualization of the non-obstructed coronary vessels. Cardiac pericytes and microvascular were observed by immunofluorescence, and the diameter of microvascular at the site of the pericyte somata was analyzed. The infarct size, and area of no-reflow in the IPC+I/R group were significantly reduced compared with the I/R group (infarct size, 33.5%±11.9% vs. 49.2%±9.4%, p=0.021；no-reflow, 12.7%±5.2% vs. 26.6%±5.0%, p<0.001). IPC improved microvascular perfusion and reduced the percentage of the blocked coronary capillary. Moreover, we found that cardiac pericytes were widely distributed around the microvascular in various regions of the heart, and expressed the contractile protein α-smooth muscle actin. The microvascular lumen diameter at pericyte somata was reduced after I/R (4.3±1.0μm vs. 6.5±1.2μm, p<0.001), which was relieved in IPC+I/R group compared with the I/R group (5.2±1.0μm vs. 4.3±1.0μm, p<0.001). Besides, IPC could reduce the proportion of apoptotic pericytes compared to the I/R group (22.1%±8.4% vs. 38.5%±7.5%, p<0.001). IPC reduced no-reflow and inhibited the contraction of microvascular pericytes induced by cardiac I/R injury, suggesting that IPC might play a protective role by regulating the pericyte function.

Implementation of Pericytes in Vascular Regeneration Strategies.

For the survival and integration of complex large-sized tissue-engineered (TE) organ constructs that exceed the maximal nutrients and oxygen diffusion distance required for cell survival, graft (pre)vascularization to ensure medium or blood supply is crucial. To achieve this, the morphology and functionality of the microcapillary bed should be mimicked by incorporating vascular cell populations, including endothelium and mural cells. Pericytes play a crucial role in microvascular function, blood vessel stability, angiogenesis, and blood pressure regulation. In addition, tissue-specific pericytes are important in maintaining specific functions in different organs, including vitamin A storage in the liver, renin production in the kidneys and maintenance of the blood-brain-barrier. Together with their multipotential differentiation capacity, this makes pericytes the preferred cell type for application in TE grafts. The use of a tissue-specific pericyte cell population that matches the TE organ may benefit organ function. In this review, we provide an overview of the literature for graft (pre)-vascularization strategies and highlight the possible advantages of using tissue-specific pericytes for specific TE organ grafts. Impact statement The use of a tissue-specific pericyte cell population that matches the tissue-engineered (TE) organ may benefit organ function. In this review, we provide an overview of the literature for graft (pre)vascularization strategies and highlight the possible advantages of using tissue-specific pericytes for specific TE organ grafts.

Sirt1 during childhood is associated with microvascular function later in life.

Microvascular dysfunction often precedes other age-related macrovascular conditions and predicts future cardiovascular risk. Sirtuin 1 (Sirt1) has recently emerged as a protein that protects the vasculature and reduces the risk of cardiovascular diseases. We tested the hypothesis that lower Sirt1 during childhood is associated with a reduced microvascular function during adulthood. Thirty-four adults (34 ± 3 yr) from the Augusta Heart Study returned to participate in the present clinical observational study. Sirt1 was assessed in samples collected during both adulthood and participants' childhood (16 ± 3 yr), and data were divided based on childhood Sirt1 concentrations: <3 ng/dL (LowCS; n = 16) and ≥3 ng/dL (HighCS; n = 18). MVF was evaluated in all of the adults using laser-Doppler flowmetry coupled with three vascular reactivity tests: 1) local thermal hyperemia (LTH), 2) post-occlusive reactive hyperemia (PORH), and 3) iontophoresis of acetylcholine (ACh). The hyperemic response to LTH was significantly (P ≤ 0.044) lower in the LowCS than in the HighCS group. Similarly, the LowCS also exhibited an ameliorated (P ≤ 0.045) response to the PORH test and lower (P ≤ 0.008) vasodilation in response to iontophoresis of ACh when compared with the HighCS. Positive relationships were identified between childhood Sirt1 and all MVF reactivity tests (r≥0.367, P ≤ 0.004). Novel observations suggest that lower Sirt1 during childhood is associated with premature microvascular dysfunction in adulthood. These findings provide evidence that Sirt1 may play a critical role in microvascular function and have therapeutic potential for the prevention of age-associated vascular dysfunction in humans.NEW & NOTEWORTHY With a longitudinal cohort, novel observations from the present study demonstrate that individuals who had lower Sirt1 early in life exhibit premature microvascular dysfunction during adulthood and may be at higher risk to develop CVD. These results provide experimental evidence that Sirt1 may play an important role in microvascular function with age and represent a potential therapeutic target to prevent premature vascular dysfunction.

Novel developments of CT: myocardial perfusion, hemodynamic assessment derived from anatomy, infarct characterization, and role of microvascular function.

Cardiac computed tomography (CT) has grown mainly based on the ability to offer a non-invasive alternative for the assessment of coronary artery stenosis, with an excellent negative predictive value for ruling out obstructive coronary artery disease (CAD). Thereafter, the technique has dramatically evolved to evaluate almost every aspect of the broad CAD spectra. Interestingly, understanding of the pathophysiology of coronary atherosclerosis has simultaneously progressed during the past decades, and CT coronary angiography (CTCA) has played a role in such development. Particularly, CTCA has contributed to change longstanding paradigms beyond ischemia detection: from a simple discrimination between patients with or without obstructive CAD; to a relatively more complex scenario consisting of patients with or without coronary atherosclerosis, patients with non-obstructive extensive/non-extensive CAD, or patients with obstructive extensive/non-extensive CAD. Furthermore, following the leading seminal role of PET-CT, dynamic perfusion CT shows promise to assess myocardial perfusion reserve comparably, being this increasingly relevant among symptomatic patients without evidence of epicardial disease.

Coronary flow reserve during dobutamine stress in Takotsubo stress cardiomyopathy

ObjectivesTakotsubo stress cardiomyopathy (TSC) is an increasingly recognised and diagnosed disease, although the underlying pathophysiology is still unknown. Our aim was to investigate the effect of the catecholamine dobutamine on...