Locational memory of macrovessel vascular cells is transcriptionally imprinted

Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems

Cardiovascular performance of adult breeding sows fails to obey allometric scaling laws

In view of the remarkable decrease of the relative heart weight (HW) and the relative blood volume in growing pigs, we investigated whether HW, cardiac output (CO), and stroke volume (SV) of modern growing pigs are proportional to BW, as predicted by allometric scaling laws: HW (or CO or SV) = a.BW(b), in which a and b are constants, and constant b is a multiple of 0.25 (quarter-power scaling law). Specifically, we tested the hypothesis that both HW and CO scale with BW to the power of 0.75 (HW or CO = a.BW(0.75)) and SV scales with BW to the power of 1.00 (SV = a.BW(1.0)). For this purpose, 2 groups of pigs (group 1, consisting of 157 pigs of 50 perpendicular to 1 kg; group 2, consisting of 45 pigs of 268 perpendicular to 18 kg) were surgically instrumented with a flow probe or a thermodilution dilution catheter, under open-chest anesthetized conditions to measure CO and SV, after which HW was determined. The 95% confidence intervals of power-coefficient b for HW were 0.74 to 0.80, encompassing the predicted value of 0.75, suggesting that HW increased proportionally with BW, as predicted by the allometric scaling laws. In contrast, the 95% confidence intervals of power-coefficient b for CO and SV as measured with flow probes were 0.40 to 0.56 and 0.39 to 0.61, respectively, and values obtained with the thermodilution technique were 0.34 to 0.53 and 0.40 to 0.62, respectively. Thus, the 95% confidence limits failed to encompass the predicted values of b for CO and SV of 0.75 and 1.0, respectively. In conclusion, although adult breeding sows display normal heart growth, cardiac performance appears to be disproportionately low for BW. This raises concern regarding the health status of adult breeding sows

Determinants of magnetic resonance imaging detected carotid plaque components: the Rotterdam Study

Aims Components of carotid atherosclerotic plaque such as intraplaque haemorrhage and lipid core are important determinants of plaque progression and destabilization. The association between plaque components and risk factors for cardiovascular disease is not well studied. Methods and results Participants from the population-based Rotterdam Study with carotid wall thickening on ultrasound (n = 1006) underwent high-resolution magnetic resonance imaging for carotid plaque characterization. Maximum wall thickening, the degree of stenosis, and the presence of intraplaque haemorrhage, lipid core, and calcification were assessed in both carotid arteries and their associations with cardiovascular risk factors were investigated. Intraplaque haemorrhage and lipid core were Conclusion In subjects from the general population with carotid wall thickening, intraplaque haemorrhage and lipid core-both considered indicators of unstable plaque-are highly frequent and more prevalent in men compared with women. Furthermore, different risk factors are associated with these plaque components: hypertension and current smoking were risk factors for the presence of intraplaque haemorrhage, and hypercholesterolaemia was the only risk factor for lipid core presence

Fatty Acid Supplementation During in vitro Embryo Production Determines Cryosurvival Characteristics of Bovine Blastocysts

In vitro production (IVP) embryos have a reduced quality and poor cryotolerance in comparison to in vivo embryos. This study investigated whether free fatty acid (FFA) conditions, fatty acid free (FAF)- synthetic oviduct fluid (SOF) without or with 25 μM of saturated stearic (C 18:0) or unsaturated oleic (C 18:1) acid during the first 5 IVP days, relate to quality and cryosurvival of day 8 blastocysts. Apart from the blastocyst scores, both 1) number and size of lipid droplets of fresh blastocysts and 2) total number and apoptotic and necrotic cells, before and after freezing-thawing, were scored by confocal microscopy. Blastocyst rates were significantly lower in the FAF SOF condition in comparison to other groups. Interestingly, blastocysts originating from the C 18:1 group, with a significantly higher lipid content, and blastocysts from the FAF SOF group demonstrated a high cryosurvival rate (70.1 and 67.4%, respectively) comparable with in vivo blastocysts (68%), in contrast to the poor cryosurvival of C 18:0 exposed embryos (17.6%). In all freeze-thawed embryos the average amount of apoptotic and necrotic cells increased albeit that the C 18:0 condition rates were higher (43.2%) when compared to C 18:1 (26.0%) and FAF SOF conditions (26.5%). The current data show that FFA administered during early embryonic development significantly affect the cryotolerance of blastocysts

Fatty Acid Supplementation During in vitro Embryo Production Determines Cryosurvival Characteristics of Bovine Blastocysts

In vitro production (IVP) embryos have a reduced quality and poor cryotolerance in comparison to in vivo embryos. This study investigated whether free fatty acid (FFA) conditions, fatty acid free (FAF)- synthetic oviduct fluid (SOF) without or with 25 μM of saturated stearic (C 18:0) or unsaturated oleic (C 18:1) acid during the first 5 IVP days, relate to quality and cryosurvival of day 8 blastocysts. Apart from the blastocyst scores, both 1) number and size of lipid droplets of fresh blastocysts and 2) total number and apoptotic and necrotic cells, before and after freezing-thawing, were scored by confocal microscopy. Blastocyst rates were significantly lower in the FAF SOF condition in comparison to other groups. Interestingly, blastocysts originating from the C 18:1 group, with a significantly higher lipid content, and blastocysts from the FAF SOF group demonstrated a high cryosurvival rate (70.1 and 67.4%, respectively) comparable with in vivo blastocysts (68%), in contrast to the poor cryosurvival of C 18:0 exposed embryos (17.6%). In all freeze-thawed embryos the average amount of apoptotic and necrotic cells increased albeit that the C 18:0 condition rates were higher (43.2%) when compared to C 18:1 (26.0%) and FAF SOF conditions (26.5%). The current data show that FFA administered during early embryonic development significantly affect the cryotolerance of blastocysts

Calcification in Major Vessel Beds Relates to Vascular Brain Disease

Objective-Calcification in atherosclerotic plaques is a novel marker of atherosclerosis and is related to cardiovascular disease. However, its relationship with cerebrovascular disease has not been investigated extensively. We investigated the relationship between calcification in various vessel beds outside the brain and imaging markers of vascular brain disease. Methods and Results-A total of 885 community-dwelling people (mean age, 66.7 years) underwent computed tomography of the coronary arteries, aortic arch, and extracranial and intracranial carotid arteries to assess arterial calcification. Brain magnetic resonance imaging scans were performed to assess cerebral infarcts, microbleeds, and white matter lesions (WMLs). Calcification in each vessel bed was associated with presence of cerebral infarcts and with larger WML volume. The most prominent associations were found between intracranial carotid calcification and WML volume and between extracranial carotid calcification and infarcts. Adjustment for cardiovascular risk factors or ultrasound carotid plaque scores did not change these results. No associations were found between calcification and cerebral microbleeds. Conclusion-Arterial calcification in major vessel beds is associated with vascular brain disease on magnetic resonance imaging. Most notably, larger intracranial carotid calcification load relates to larger WML volumes, and larger extracranial carotid calcification load relates to the presence of cerebral infarcts, independently of ultrasound carotid plaque score. This suggests that calcification of atherosclerotic plaque yields other information in addition to merely the presence of plaques, providing novel insights into the etiology of vascular brain disease. (Arterioscler Thromb Vasc Biol. 2011;31:2331-2337.