Increasing evidence links metabolism, protein synthesis, and growth signaling to impairments in the function of hematopoietic stem and progenitor cells (HSPC) during aging. The Lin28b/Hmga2 pathway controls tissue development and the postnatal downregulation of this pathway limits the self-renewal of adult vs. fetal hematopoietic stem cells (HSC). Igf2bp2 is an RNA binding protein downstream of Lin28b/Hmga2, which regulates mRNA stability and translation. The role of Igf2bp2 in HSC aging is unknown. Here, we show in an analysis of wildtype and Igf2bp2 knockout mice that Igf2bp2 regulates oxidative metabolism in HSPC and the expression of metabolism, protein synthesis, and stemness-related genes in HSC of young mice. Interestingly, Igf2bp2 expression and function strongly decline in HSC aging. In young mice, Igf2bp2-deletion mimics aging-related changes of HSC, including changes in Igf2bp2-target gene expression and the impairment in colony formation and repopulation capacity. In aged mice, Igf2bp2 gene status has no effect on these parameters in HSC. Unexpectedly, Igf2bp2 deficient mice exhibit an amelioration of the aging-associated increase of HSC numbers and myeloid skewed differentiation. Together, Igf2bp2 controls mitochondrial metabolism, protein synthesis, growth, and stemness of young HSC, which is required for full HSC function at young adult age. However, Igf2bp2 gene function is lost during aging and it appears to contribute to HSC aging in two ways: (i) the aging-related loss of Igf2bp2 gene function impairs the growth and repopulation capacity of aging HSC and (ii) the activity of Igf2bp2 at young age contributes to aging-associated HSC expansion and myeloid skewing.

Type III collagen plays an important role in activating platelets, forming thrombus, and maintaining the mechanical properties of arteries. This study aimed to test the hypothesis that genetic variants of COL3A1 (gene encoding type III collagen) contribute to recurrence and prognosis of stroke. We investigated the associations of three variants (rs2138533, rs11887092, and rs1800255) in the COL3A1 gene with stroke recurrence and prognosis in 1,544 patients with three subtypes of stroke: lacunar infarction (n = 442), atherothrombotic infarction (n = 670), and hemorrhage (n = 432). These associations were evaluated by Kaplan-Meier analysis and Cox regression models. Patients were followed up for 4.5 years. The A allele of rs1800255 in the COL3A1 gene coding region was significantly associated with a reduced risk of stroke recurrence in patients with lacunar infarction (adjusted hazard ratio [HR] 0.58, 95 % confidence interval [CI] 0.36-0.93, P = 0.024), but there was an increased risk of all-cause mortality of atherothrombotic patients (adjusted HR 1.43, 95 % CI 1.01-2.00, P = 0.044). The TT genotype of rs2138533 showed a significantly increased risk of death caused by cardiovascular disease or stroke in lacunar infarct patients (adjusted HR 2.98, 95 % CI 1.27-6.98, P = 0.012), but there was a reduced risk of all-cause mortality for patients with intracerebral hemorrhage (adjusted HR 0.34, 95 % CI 0.12-0.93, P = 0.036). The G allele of rs11887092 increased the risk of stroke recurrence in patients with atherothrombotic stroke (adjusted HR 1.59, 95 % CI 1.04-2.44, P = 0.035). In conclusion, variants of COL3A1 might play a vital role in determining the risk of recurrence and prognosis after stroke.

Background and purpose: This study aimed to test the hypothesis that long noncoding RNA (lncRNA) AL110200 exerts a proinflammatory effect on atherosclerosis and that the variant rs901681 contributes to ischaemic stroke incidence and recurrence. Methods:The expression of AL110200 was analyzed in THP-1 cells treated with oxidized low-density lipoprotein and in human peripheral blood in a coronary heart disease and control population to determine the role of AL110200 in atherosclerosis. The effect of AL110200 on cell adhesion and invasion was tested. The plasma level of leukotriene B4 and rs901681 genotype distribution were assessed in 220 participants. In 1004 ischaemic stroke patients and 1434 controls, the association between rs901681 and stroke incidence was analyzed by logistic regression, and the association of rs901681 and stroke prognosis was analyzed using Kaplan-Meier analysis and the Cox proportional hazards model.Results: Increased expression of AL110200 was observed in THP-1 cells under oxidized low-density lipoprotein treatment. Knockdown of AL110200 reduced the adhesive and invasive ability of THP-1 cells. AL110200 expression in peripheral blood was significantly higher in the coronary heart disease group than in the controls. The GG genotype of rs901681 is associated with reduced plasma leukotriene B4. In the ischaemic stroke population, rs901681 was not associated with ischaemic stroke incidence (p = 0.686).Patients carrying rs901681 GG had a lower risk for stroke recurrence at age ≥60 years (p = 0.001), cardiovascular stroke death (p = 0.022) and all-cause mortality (p = 0.034) in the all-age group.Conclusions: AL110200 might exert a proinflammatory effect on atherosclerosis, and the variant rs901681 might be a strong predictor of stroke prognosis in ischaemic stroke patients.

Object. Variants of Kallikreins have been shown to be risk factors for intracranial aneurysm (IA) in a Finnish population. In the present study, the authors investigated the correlation between polymorphisms in the Kallikrein gene cluster and IAs in the Chinese population.Methods. The association of Kallikrein variants (rs1722561 and rs1701946) with sporadic IAs was tested in 308 cases and 443 controls. The differences in allelic frequencies between patients and the control group were evaluated with the chi-square test.Results. The C allele of rs1722561 showed a significant reduction in the risk of sporadic IA (OR 0.71, 95% CI 0.53-0.95; p = 0.023). However, no association of the variant rs1701946 with sporadic IA was found (OR 0.78, 95% CI 0.57-1.06; p = 0.115).Conclusions. The variant rs1722561 of Kallikreins might reduce the risk of sporadic IAs among individuals of Chinese Han ethnicity. This study confirms the association between Kallikreins and IAs.