Recent studies have revealed an inverse association between height and cardiovascular disease. However, the background mechanism of this association has not yet been clarified. Height has also been reported to be positively associated with cancer. Therefore, well-known cardiovascular risk factors, such as increased oxidative stress and chronic inflammation, are not the best explanations for this inverse association because these risk factors are also related to cancer. However, impaired blood flow is the main pathological problem in cardiovascular disease, while glowing feeding vessels (angiogenesis) are the main characteristic of cancer pathologies. Therefore, endothelial maintenance activity, especially for the productivity of hematopoietic stem cells such as CD34-positive cells, could be associated with the height of an individual because this cell contributes not only to the progression of atherosclerosis but also to the development of angiogenesis. In addition, recent studies have also revealed a close connection between bone marrow activity and endothelial maintenance; bone marrow-derived hematopoietic stem cells contribute towards endothelial maintenance. Since the absolute volume of bone marrow is positively associated with height, height could influence endothelial maintenance activity. Based on these hypotheses, we performed several studies. The aim of this review is not only to discuss the association between height and bone marrow activity, but also to describe the potential mechanism underlying endothelial maintenance. In addition, this review also aims to explain some of the reasons that implicate hypertension as a major risk factor for stroke among the Japanese population. The review also aims to clarify the anthropological reasons behind the high risk of atherosclerosis progression in Japanese individuals with acquired genetic characteristics.
Aged ; Atherosclerosis/physiopathology* ; Body Height/physiology* ; Bone Marrow/physiology* ; Disease Progression ; Endothelium/physiology* ; Humans ; Hypertension/physiopathology* ; Japan/epidemiology* ; Male ; Middle Aged ; Risk Factors ; Stroke/physiopathology*

Atherosclerotic cardiovascular disease (ASCVD) is the deadliest disease in the world, with endothelial injury occurring throughout the course of the disease. Therefore, improvement in endothelial function is of essential importance in the prevention of ASCVD. Red yeast rice (RYR), a healthy traditional Chinese food, has a lipid modulation function and also plays a vital role in the improvement of endothelial reactivity and cardiovascular protection; thus, it is significant in the prevention and treatment of ASCVD. This article reviews the molecular mechanisms of RYR and its related products in the improvement of endothelial function in terms of endothelial reactivity, anti-apoptosis of endothelial progenitor cells, oxidative stress alleviation and anti-inflammation.
Apoptosis ; drug effects ; Atherosclerosis ; pathology ; physiopathology ; prevention & control ; Biological Products ; chemistry ; pharmacology ; therapeutic use ; Cardiovascular Diseases ; pathology ; physiopathology ; prevention & control ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Endothelium, Vascular ; cytology ; drug effects ; physiology ; Humans ; Inflammation ; prevention & control ; Lipid Metabolism ; drug effects ; Oxidative Stress ; drug effects

Adult ; Atherosclerosis ; diagnosis ; Chest Pain ; Coronary Aneurysm ; diagnosis ; Coronary Angiography ; Coronary Artery Disease ; diagnostic imaging ; Coronary Vessel Anomalies ; diagnosis ; Coronary Vessels ; diagnostic imaging ; physiopathology ; Electrocardiography ; Humans ; Male ; Risk Factors ; Troponin I ; metabolism ; Vascular Diseases ; congenital ; diagnosis

OBJECTIVETo compare the efficacy between acupuncture at stellate ganglion combined with intravenous administration of alprostadil and simple intravenous administration of alprostadil on lower limb atherosclerosis of early diabetes mellitus.

METHODSSixty patients of lower limb atherosclerosis of early diabetes mellitus were randomly divided into an observation group and a control group, 30 cases in each one. Patients in the two groups were treated with basic treatment to control blood glucose and lipid. In addition, patients in the control group were treated with intravenous administration of alprostadil (10 µg) and sodium chloride solution (100 mL); based on this, patients in the observation group were treated with acupuncture at stellate ganglion. The treatment was given once a day; the consecutive treatment of two weeks constituted one session, and totally 4 sessions were given. The total syndrome score, glycosylated hemoglobin (HbA1c), blood flow of posterior tibial artery and dorsal artery of foot were observed before and after treatment; the clinical efficacy was compared between the two groups.

RESULTSCompared before treatment, the total syndrome score, HbA1c, blood flow of posterior tibial artery and dorsal artery of foot were significantly improved after treatment (all P < 0.05), which were more obvious in the observation group (all P < 0.05). After treatment, the total effective rate was 93.3% (28/30) in the observation group, which was significantly superior to 86.7% (26/30) in the control group (P < 0.05). CONCLUSION Acupuncture at stellate ganglion combined with intravenous administration of alprostadil achieve better effect than simple intravenous administration of alprostadil for lower limb atherosclerosis of early diabetes mellitus, which improve the clinical symptoms, regulate blood sugar and increase the blood flow of lower limb.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Atherosclerosis ; etiology ; physiopathology ; therapy ; Diabetes Mellitus, Type 2 ; complications ; Female ; Humans ; Lower Extremity ; blood supply ; innervation ; physiopathology ; Male ; Middle Aged ; Stellate Ganglion ; physiopathology ; Treatment Outcome

Gap junctions play a critical role in electrical synchronization and exchange of small molecules between neighboring cells; connexins are a family of structurally related transmembrane proteins that assemble to form vertebrate gap junctions. Hyperglycemia changes the structure gap junction proteins and their expression, resulting in obstruction of neural regeneration, vascular function and wound healing, and also promoting vascular atherosclerosis. These pathogenic factors would cause diabetic foot ulcers. This article reviews the involvement of connexins in pathogenesis of diabetic foot.
Atherosclerosis ; Connexins ; metabolism ; Diabetic Foot ; pathology ; Gap Junctions ; metabolism ; Humans ; Hyperglycemia ; physiopathology ; Regeneration ; Wound Healing

BACKGROUNDAutophagy has been found to be involved in animal and cell models of atherosclerosis, but to date, it lacks general observation in human atherosclerotic plaques. Here, we investigated autophagy in smooth muscle cells (SMCs), endothelial cells (ECs), and macrophages in human atherosclerotic plaques via transmission electron microscopy (TEM), western blotting, and immunohistochemistry analysis.

METHODSThe histopathologic morphology of these plaques was observed via hematoxylin and eosin staining. The ultrastructural morphology of the SMCs, ECs, and macrophages in these plaques was observed via TEM. The localization of microtubule-associated protein 1 light chain 3 (MAP1-LC3), a relatively special maker of autophagy, in plaques was observed by double fluorescent immunochemistry and western blotting.

RESULTSAll of these human atherosclerotic plaques were considered advanced and unstable in histologically observation. By double fluorescent immunochemistry, the expression of LC3-II increased in the SMCs of the fibrous cap, the macrophages, and the microvascular ECs of the plaque shoulders. The protein level of LC3-II by western blotting significantly increased in plaques compared with normal controls. In addition, TEM observation of plaques revealed certain features of autophagy in SMCs, ECs, and macrophages including the formation of myelin figures, vacuolization, and the accumulation of inclusions in the cytosol. These results indicate that autophagy is activated in SMCs, ECs, and macrophages in human advanced atherosclerotic plaques.

CONCLUSIONSOur study is to demonstrate the existence of autophagy in human atherosclerotic plaques by different methods, which may contribute to the development of pharmacological approaches to stabilize vulnerable and rupture-prone lesions.

Atherosclerosis ; metabolism ; physiopathology ; Autophagy ; physiology ; Endothelial Cells ; pathology ; Humans ; In Vitro Techniques ; Microscopy, Electron, Transmission ; Microtubule-Associated Proteins ; metabolism ; Myocytes, Smooth Muscle ; pathology ; Plaque, Atherosclerotic ; metabolism ; physiopathology ; ultrastructure

Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family. As a novel adipokine, it widely presents in the tissues under the condition of metabolic disorders. More and more studies suggest that NGAL might be a marker for a variety of diseases associated with lipid metabolism. It is likely that NGAL plays an important role in obese-inflammation-induced metabolic syndrome,insulin resistance, glucose and lipid metabolism, endothelial dysfunction and atherosclerosis pathway.
Acute-Phase Proteins ; metabolism ; Atherosclerosis ; Biomarkers ; metabolism ; Humans ; Inflammation ; Insulin Resistance ; Lipocalin-2 ; Lipocalins ; metabolism ; Metabolic Syndrome ; metabolism ; physiopathology ; Obesity ; Proto-Oncogene Proteins ; metabolism

OBJECTIVETo investigate the effects of simvastatin on atherosclerosis and central aortic pressure in ApoE-knockout (ApoE-/-) mice.

METHODSTen 5-week-old male ApoE-/- mice and 5 C57 mice were fed with high-lipid diet for 3 weeks, and then C57 mice (WT group) and 5 ApoE-/- mice (ApoE-/- group) were given 1% carboxymethyl cellulose solution (8 ml·kg-1·d-1), and another 5 ApoE-/- mice (ApoE-/-/S group) were given simvastatin solution (50 mg·kg-1·d-1) by gavege for 3 weeks. The areas of atherosclerotic lesion in aortic root, central aortic pressure and serum lipid levels were examined.

RESULTSNo atherosclerotic plaques were observed in WT group. Compared with ApoE-/- group, simvastatin significantly decreased atherosclerotic lesion area in aortic root (89 818.05±16 980.93 μm2 vs 34 937.01±13 280.65 μm2, P<0.05). The systolic pressure (SP), mean arterial pressure (MAP), pulse pressure (PP) and diastolic pressure (DP) of central aortic pressure were significantly increased in ApoE-/- group compared with those in WT group (P<0.05). Compared to ApoE-/- group, the SP, MAP and PP of central aortic pressure were significantly reduced in ApoE-/-/S group (P<0.05). SP and MAP of central aortic pressure were positively correlated with atherosclerotic lesion area (SP: r=0.7152, P=0.0461; PP: r=0.7594， P=0.0288). Compared with WT group, serum triglyceride, total cholesterol and low-density lipoprotein levels were markedly increased in ApoE-/- group (P<0.05). Serum high-density lipoprotein level was decreased in ApoE-/- group compared with WT group. No differences in serum triglyceride, total cholesterol, low-density lipoprotein and high-density lipoprotein levels were found between ApoE-/- group and ApoE-/-/S group.

CONCLUSIONSimvastatin can attenuate atherosclerosis of aorta in ApoE-/- mice, which is associated with the reduced central aortic systolic pressure but not with the serum lipids levels.

Animals ; Apolipoproteins E ; genetics ; Arterial Pressure ; drug effects ; Atherosclerosis ; drug therapy ; genetics ; physiopathology ; Cholesterol ; blood ; Disease Models, Animal ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Male ; Mice ; Mice, Knockout ; Simvastatin ; pharmacology ; Triglycerides ; blood

OBJECTIVETo investigate the effects of non-neuronal muscarinic receptors (NNMR) stimulation on atherosclerosis and endothelial cells activation.

METHODSAtherosclerosis model was established in ApoE-/- mice by a high fat diet for 7 weeks. During the experimental periods, animals were received a low (7 mg/kg/d) or a high (21 mg/kg/d) dose of arecoline by gavage. At the termination of the treatments, serum total cholesterol and NO levels were measured, and the aorta morphology was analyzed by hematoxylin and eosin staining. The gene expression of monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules in the thoracic aortas was determined by RT-PCR, and the MCP-1 protein expression and NF-κB activity were detected by Western blot analysis. NO production, MCP-1 secretion in cultured rat aortic endothelial cells (RAECs), and monocyte-endothelium adhesion assay were also performed after arecoline treatments.

RESULTSArecoline efficiently decreased atherosclerotic plaque areas, increased serum nitric oxide (NO) content, suppressed the mRNA and protein expression of MCP-1, and modulated the IκB-α degradation and P65 phosphorylation in the aortae of ApoE-/- mice. Furthermore, arecoline promoted NO production and suppressed MCP-1 secretion in cultured RAECs after ox-LDL exposure, and either atropine or NG-nitro-L-arginine methylester could abrogate these effects. Arecoline also significantly inhibited the adherence of U937 monocytes to the ox-LDL injured human umbilical vein endothelial cells, which could be abolished by atropine.

CONCLUSIONOur results indicate that arecoline attenuates the progression of atherosclerosis and inhibits endothelial cells activation and adherence by stimulating endothelial NNMR. These effects, at least in part, are due to its modulation on NF-κB activity.

Animals ; Aorta ; cytology ; Apolipoproteins E ; Arecoline ; pharmacology ; Atherosclerosis ; physiopathology ; prevention & control ; Cell Adhesion Molecules ; metabolism ; Chemokine CCL2 ; metabolism ; Cholesterol ; blood ; Disease Progression ; Endothelial Cells ; cytology ; drug effects ; Endothelium, Vascular ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; I-kappa B Proteins ; metabolism ; Lipoproteins, LDL ; Mice ; Mice, Knockout ; Monocytes ; cytology ; NF-KappaB Inhibitor alpha ; Nitric Oxide ; blood ; Nitroarginine ; pharmacology ; Rats ; Receptors, Muscarinic ; physiology ; Transcription Factor RelA ; metabolism

OBJECTIVE: To determine the association between carotid atherosclerosis and renal function in hypertensive patients. METHODS: A total of 2 809 hypertensive patients aged (56.59±10.79) years were enrolled. Carotid intima-media thickness (cIMT) was derived via B-mode ultrasonography and chronic kidney disease (CKD) was evaluated by the estimated glomerular filtration rate (eGFR) with Cockcroft- Gault method. The patients were divided into 3 groups: a normal group, a thick group, and a plaque group according to the results of carotid ultrasonography. RESULTS: The eGFR of the normal group was (111.09±25.61) mL/(min.1.73m(2)), that of the thick group and the plaque group was (94.45±27.14) mL/(min.1.73m(2)) and (85.98±26.92) mL/ (min.1.73m(2)). Binary logistic analysis showed that age (OR=3.590), smoking status (OR=1.543), systolic blood pressure (OR=1.018), diastolic blood pressure (OR=0.977), fasting plasma glucose (OR=1.132), triglyceride (OR=0.873) and eGFR (OR=0.986) were significantly correlated with cIMT. Subgroup analyses on different genders showed that eGFR was a significant independent risk factor in men (OR=0.991) but not in women. CONCLUSION The thicker the cIMT, the lower the eGFR in hypertensive patients. With the development of cIMT, eGFR gradually decreases and contributes to the occurrence and development of early-stage atherosclerosis in hypertensive patients.
Aged ; Atherosclerosis ; Blood Pressure ; Carotid Arteries ; diagnostic imaging ; pathology ; Carotid Artery Diseases ; Carotid Intima-Media Thickness ; Female ; Glomerular Filtration Rate ; Humans ; Hypertension ; physiopathology ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; Risk Factors ; Smoking