Dental Pulp Mesenchymal Stem Cells Attenuate Limb Ischemia via Promoting Capillary Proliferation and Collateral Development in a Preclinical Model

Critical limb ischemia (CLI), an end-stage manifestation of peripheral artery disease (PAD), still lacks effective therapeutic strategies. Recently, dental pulp-derived mesenchymal stem cells (DP-MSCs) have been attracting more and more attentions in therapeutic applications due to their high proliferation ability, powerful osteogenic differentiation potential, and effective anti-inflammatory effects. In this study, we compared the therapeutic effects of MSCs derived from different sources in a femoral artery-ligated preclinical ischemic model. We found that treatments with MSCs, including bone marrow- (BM-), adipose- (AD-), dental pulp- (DP-), and umbilical cord- (UC-) derived MSCs, improved limb functions, reduced inflammatory responses, increased angiogenesis, and promoted regeneration of muscle fiber. Among them, DP-MSCs and BM-MSCs produced much more impressive effects in restoring limb functions and promoting angiogenesis. The flow velocity restored to nearly 20% of the normal level at 3 weeks after treatments with DP-MSCs and BM-MSCs, and obvious capillary proliferation and collateral development could be observed. Although neovascularization was induced in the ischemic limb after ligation, MSCs, especially DP-MSCs, significantly enhanced the angiogenesis. In vitro experiments showed that serum deprivation improved the expression of angiogenic factors, growth factors, and chemokines in DP-MSCs and UC-MSCs, but not in BM-MSCs and AD-MSCs. However, DP-MSCs produced stronger therapeutic responses than UC-MSCs, which might be due to the higher expression of hepatocyte growth factor (HGF) and hypoxia-inducible factor-1 α (HIF-1α). We speculated that DP-MSCs might stimulate angiogenesis and promote tissue repair via expressing and secreting angiogenic factors, growth factors, and chemokines, especially HGF and HIF-1α. In conclusion, DP-MSCs might be a promising approach for treating CLI.

Visfatin and 25-Hydroxyvitamin D3 Levels Affect Coronary Collateral Circulation Development in Patients with Chronic Coronary Total Occlusion

Background: Coronary collateral circulation (CCC) plays a vital role in the myocardial blood supply, especially forischemic myocardium. Evidence suggests that the visfatin and 25-hydroxyvitamin D3 [25(OH)D3] levels are related to the degree and incidence of vascular stenosis associated with coronary artery disease; however, few studies have evaluated the effect of visfatin and 25(OH)D3 on CCC development in patients with chronic total occlusion (CTO).This study aimed to evaluate the relationship between the serum visfatin and 25(OH)D3 levels and CCC in patients with CTO.Methods: A total of 189 patients with CTO confirmed by coronary angiography were included. CCC was graded from 0 to 3 according to the Rentrop-Cohen classification. Patients with grade 0 or grade 1 collateral development were included in the poor CCC group (n = 82), whereas patients with grade 2 or grade 3 collateral development were included in the good CCC group (n = 107). The serum visfatin and 25(OH)D3 levels were measured by ELISA.Results: The visfatin level was significantly higher in the poor CCC group than in the good CCC group, and the 25(OH)D3 level was significantly lower in the poor CCC group than in the good CCC group (P = 0.000). Correlation analysis showed that the Rentrop grade was negatively correlated with the visfatin level (r = − 0.692, P = 0.000) but positively correlated with the 25(OH)D3 level (r = 0.635, P = 0.000). Logistic regression analysis showed that the visfatin and 25(OH)D3 levels were independent risk factors for CCC (odds ratio 1.597, 95% confidence interval 1.300–1.961, P = 0.000 and odds ratio 0.566, 95% confidence interval 0.444–0.722, P = 0.000, respectively). The visfatin and25(OH)D3 levels can effectively predict the CCC status.Conclusion: Serum visfatin and 25(OH)D3 levels are related to CCC development and are independent predictors of poor CCC.

Exercise Training as a Mediator for Enhancing Coronary Collateral Circulation: A Review of the Evidence

: Coronary collateral vessels supply blood to areas of myocardium at risk after arterial occlusion. Flow through these channels is driven by a pressure gradient between the donor and the occluded artery. Concomitant with increased collateral flow is an increase in shear force, a potent stimulus for collateral development (arteriogenesis). Arteriogenesis is self-limiting, often ceasing prematurely when the pressure gradient is reduced by the expanding lumen of the collateral vessel. After the collateral has reached its self-limited maximal conductance, the only way to drive further increases is to re-establish the pressure gradient. During exercise, the myocardial oxygen demand is increased, subsequently increasing coronary flow. Therefore, exercise may represent a means of driving augmented arteriogenesis in patients with stable coronary artery disease. Studies investigating the ability of exercise to drive collateral development in humans are inconsistent. However, these inconsistencies may be due to the heterogeneity of assessment methods used to quantify change. This article summarises current evidence pertaining to the role of exercise in the development of coronary collaterals, highlighting areas of future research.

Assessment of neutrophil and neutrophil/lymphocyte ratio in coronary collateral developed patients with acute coronary syndrome

SUMMARY OBJECTIVE Inflammation-related markers provide diagnostic and prognostic information for coronary artery disease and acute coronary syndrome. We aimed to compare neutrophil count and neutrophil/lymphocyte ratio (NLR) in acute coronary syndrome patients with coronary collateral development in our study. METHODS A total of 426 patients (102 unstable angina pectoris (USAP), 223 non-ST-elevation myocardial infarction (non-STEMI), 103 ST-elevation myocardial infarction (STEMI) were compared regarding hemoglobin, platelet, lymphocyte, neutrophil count, and NLR. RESULTS Neutrophil count and NLR were significantly lower in USAP patients and higher in STEMI patients; 5.14± 1.79 vs. 7.21± 3.05 vs. 9.93±4.67 and 2.92±2.39 vs. 5.19±4.80 vs. 7.93±6.38, p <0.001. Other parameters, i.e., hemoglobin, platelet, and lymphocyte count, were not significantly different between the groups. CONCLUSIONS In our study, it was concluded that there may be a statistically significant difference in the number of neutrophil counts and NLR among the types of acute coronary syndromes with coronary collateral development.

Abstract TP93: Rapid and Appropriate Evaluation of Collateral Development by Four-Dimensional CT Angiography Covering Only 4-cm Width With a Focus on the Intracranial Internal Carotid Artery and the Middle Cerebral Artery to Identify Candidates of Thrombectomy

Introduction: Four-dimensional computed tomography (CT) angiography (4D-CTA) can visualize time sequential changes of bilateral internal carotid (ICA) and middle cerebral arteries (MCA). Therefore, 4D-CTA could find ICA or MCA occlusion and visualize collateral circulation in case of intracranial artery occlusion. Hypothesis: Four-dimensional CTA covering only 4-cm width with a focus on the intracranial ICA and the MCA can early visualize them because of small volumetric data and evaluate collateral development status to identify candidates of thrombectomy. Methods: We included acute ischemic stroke patients who 1) were admitted from August 2018 to July 2019 due to ICA or MCA occlusion, 2) underwent 4D-CTA covering only 4-cm width on admission and 3) underwent endovascular thrombectomy. We classified collateral status into good, moderate and poor collateral according to opacification of M2 and M3 branches distal to occlusion and evaluated successful recanalization of thrombolysis in cerebral infarction (TICI) grade 2b or 3 and improvement of NIHSS score 7 days after thrombectomy. Results: During the study period, 337 acute ischemic stroke patients were admitted, 92 patients suffered from ICA or MCA occlusion and 23 patients met our inclusive criteria. Median age was 81 years and median ASPECTS was 10. Image reconstruction time of 1,000 images was only 69 seconds and 4D-CTA with only 4-cm width demonstrated MCA occlusion in 14 patients, IC occlusion in 9 patients and collateral status as good in 4 patients, moderate in 13 patients and poor in 6 patients. Median onset-to-recanalization time was 5.2 hours, successful recanalization was achieved in 21 patients (91.3%), median NIHSS score on admission was 20, median 7-day NIHSS score decreased to 6 (p<0.0001) and median decrease of NIHSS score was 13. Two patients without successful recanalization had no early improvement of NIHSS score, whereas 20 of 21 patients with successful recanalization obtained early neurological improvement. Conclusion: Four-dimensional CTA with only 4-cm width rapidly and appropriately evaluated collateral status to identify candidates of thrombectomy for ICA or MCA occlusion and achieved early neurological improvement following successful recanalization.