Endogenous bioactive small molecules are characterized by low molecular weight,high biological activity,low immunogenicity,and rapid synthesis and metabolism,play a pivotal role in maintaining vascular homeostasis.Vascular calcification(VC)is a abnormal deposition of calcium and phosphorus in the vessel wall.Endogenous bioactive small molecules such as cardiovascular bioactive peptides,adipokines and gaseous molecules participate in the process of VC through various mechanisms.This review summarises the advances in relationship between endogenous bioactive small molecules and the occurrence,development,and related mechanisms of VC.

Endogenous bioactive small molecules are characterized by low molecular weight,high biological activity,low immunogenicity,and rapid synthesis and metabolism,play a pivotal role in maintaining vascular homeostasis.Vascular calcification(VC)is a abnormal deposition of calcium and phosphorus in the vessel wall.Endogenous bioactive small molecules such as cardiovascular bioactive peptides,adipokines and gaseous molecules participate in the process of VC through various mechanisms.This review summarises the advances in relationship between endogenous bioactive small molecules and the occurrence,development,and related mechanisms of VC.

Objective:To investigate the clinical features, diagnosis and treatment of lymphoplasmacytic lymphoma (LPL) with biclonal M protein.Methods:The clinical data of one LPL patient with biclonal M protein at Yancheng First People's Hospital in January 2018 was retrospectively analyzed, and relevant literature was reviewed.Results:The patient was an elderly woman with clinical manifestations of lymphadenopathy, kidney damage, anemia, and bone destruction. The diagnosis was confirmed based on lymph node biopsy, immunofixation electrophoresis, bone marrow cytology, and genetic mutation testing (MYD88 L265P mutation-positive). Partial remission was achieved after 4 courses of treatment with bortezomib-based regimen.Conclusions:Clinically, LPL with biclonal M protein shows one characteristic of M protein, and the immunoglobulin IgM and IgA biclonal LPL is even rarer. The treatment scheme based on bortezomib has a certain therapeutic effect.

Objective To examine the effects of exogenously administered intermedin (IMD,adrenomedullin-2) on arterial blood pressure,cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats (SHRs) as well as to investigate the associated mechanisms.Methods Thirteen week-old male rats were divided in Wistar Kyoto (WKY) group (n =12),SHR group (n =12),IMD group (SHRs infused with IMD 1-47 500 ng/kg per hour,n =12),and ADM group (SHRs infused with adrenomedullin 500 ng/kg per hour,n =12).Results A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure,the maximal rates of increase and decrease of left-ventricle pressure development (LV ± dp/dtmax),left ventricular systolic pressure and heart rate in SHRs.Furthermore,IMD also inhibited protein over-expression of cardiovascular IMD receptors,myocardial Receptor Activity-Modifying Proteins (RAMP1 and RAMP2),aortic RAMP1,RAMP2,RAMP3,and calcitonin receptor-like receptor (CRLR);suppressed up-regulation of aortic RAMP1,RAMP2,RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide (ANP) and myocardial brain natriuretic peptide (BNP).Additionally,IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration.Conclusion These findings support the speculation that IMD,as a cardiovascular active peptide,is involved in blood pressure reduction and cardiac function amelioration during hypertension.The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR,and consequential regulation of cAMP levels and other cardiovascular active factors,such as ANP and BNP.

Objective To test the hypothesis that IL-10 may promoting left ventricular remodeling and cardiac function by modulating extracellular matrix after acute myocardial infarction. Methods Male adult rats were randomly divided into three groups: control group (n=6) , MI/AAV2 group (n=16) and MI/AAV2-IL-10 group (n=16). Establishing animal modol of experimental myocardial infarction and recombinant adeno-associated virus type 2 (AAV)/IL-10 (AAV2-rhIL-10) and AAV2 were injected around the ischemic zone. Echocardiography parameters, hemodynamic parameters, left ventricular mass index (LVMI) , collagen volume fraction (CVF) , perivascu-lar circumferential area (PVCA) , collagen type Ⅰ & Ⅲ volume fraction and mRNA levels of collagen type Ⅰ & Ⅲ , matrix metalloproteinases-2 ( MMP-2 ) and tissue inhibitor of metalloproteinase-1 ( TIMP-1) were compared among the three groups. Results Improved cardiac function was observed in MI/AAV2-IL-10 group shown by echocardiography and hemodynamic examination. Four weeks after myocardial infarction, thickness of different parts of LV was not different in MI/AAV2-IL-10 group and MI/AAV2 group. Nevertheless CVF, PVCA and collagen type Ⅰ volume fraction was significantly descending in remote zone of MI/AAV2-IL-10 group compared with that of MI/ AAV2 group. The mRNA expression of collagen type I and MMP-2 was lower in MI/AAV2-IL-10 group than that in MI/AAV2 group. Conclusion Recombinant IL-10 expression mediated by AAV2-rhIL-10 transfection of rats' myocardium promotes LV remodeling and cardiac function after acute myocardial infarction. The promotion was partially achieved by inhibition myocardium collagen deposition.

The endoplasmic reticulum (ER) serves several important functions, mainly post-translational modification, folding and assembly of newly synthesized secretary proteins, synthesizing lipids and cellular calcium storage. Various factors can disrupt ER homeostasis and disturb its functions, which leads to the accumulation of unfolded and misfolded proteins and to potential cellular dysfunction and pathological consequences, collectively termed ER stress. Recent progress suggests that ER stress plays a key role in the immune response, diabetes, tumor growth, and some neurodegenerative diseases. In particular, ER stress is involved in several processes of cardiovascular diseases, such as ischemia/reperfusion injury, cardiomyopathy, cardiac hypertrophy, heart failure, and atherosclerosis. Further research on the relation of ER stress to cardiovascular diseases will greatly enhance the understanding of these pathological processes and provide novel avenues to potential therapies.

Objective To investigate the role of endogenous Hydrogen Sulfide (H2S) in airway inflammation and responsiveness in a rat model of chronic passive-smoking.Methods Male SD rats were randomly divided into a control group (breathing fresh air) and a passive smoking group [cigarette smoking (CS) passively] ,with 18 rats in each group.Six rats in each group were randomly intraporitoneally injected with normal saline, sodium hydrosulfide (NailS) or propargylglycine (PPG, an irreversible inhibitor of cystathionine-γ-lyase).The animals were divided into six subgroups,ie.Con group, Naris group, and PPG group, CS group, CS + Naris group, and CS + PPG group.After 4 months,lung histological change and airway tension were measured.The H2 S levels of plasma and lung tissue were analyzed by the sensitive sulphur electrode assay.The expression of cystathionine-γ-lyase (CSE) was measured by western blot.Results Compared with the Con group, CSE protein expression in lung tissues was increased in CS group(P < 0.05) ; the H2S levels of plasma were significantly higher in GS group,NariS group and CS + Naris group,and much lower in PPG group (P < 0.05, respectively).Compared with CS group, the H2 S levels of plasma were significantly higher in CS + Naris group, and much lower in CS + PPG group (P < 0.05, respectively).The H2S level of lung tissue in each group had no significant difference (P > 0.05).Compared with Con group, score of lung pathology was significant elevated, and the responsiveness of airway smooth muscles to Ach and KCI was significant augmented in CS group.Compared with CS group, the score of lung pathology was decreased, and the responsiveness of airway smooth muscles was decreased in CS + NariS group(P < 0.05), and vise versa in CS + PPG group (P < 0.01).Conclusion H2 S can alleviate airway inflammation and hyperresponsiveness induced by CS, and administration of H2S might be of clinical benefit in airway inflammation and airway responsiveness.

Objective To test the hypothesis that IL-10 may promoting left ventricular remodeling and cardiac function by modulating extracellular matrix after acute myocardial infarction. Methods Male adult rats were randomly divided into three groups:control group (n=6),MI/AAV2 group (n=16) and MI/AAV2-IL-10 group (n=16). Establishing animal modol of experimental myocardial infarction and recombinant adeno-associated virus type 2 (AAV)/IL-10 (AAV2-rhIL-10) and AAV2 were injected around the ischemic zone. Echocardiography parameters,hemodynamic parameters,left ventricular mass index (LVMI),collagen volume fraction (CVF),perivascular circumferential area (PVCA),collagen type Ⅰ&Ⅲ volume fraction and mRNA levels of collagen type Ⅰ&Ⅲ,matrix metalloproteinases-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were compared among the three groups. Results Improved cardiac function was observed in MI/AAV2-IL-10 group shown by echocardiography and hemodynamic examination. Four weeks after myocardial infarction,thickness of different parts of LV was not different in MI/AAV2-IL-10 group and MI/AAV2 group. Nevertheless CVF,PVCA and collagen type Ⅰ volume fraction was significantly descending in remote zone of MI/AAV2-IL-10 group compared with that of MI/AAV2 group. The mRNA expression of collagen type I and MMP-2 was lower in MI/AAV2-IL-10 group than that in MI/AAV2 group. Conclusion Recombinant IL-10 expression mediated by AAV2-rhIL-10 transfection of rats' myocardium promotes LV remodeling and cardiac function after acute myocardial infarction. The promotion was partially achieved by inhibition myocardium collagen deposition.

Objective To examine whether the two vascular paracrine/autocrine factors, angiotensin Ⅱ (Ang Ⅱ) and endothelin, participate in the pathogenesis of arterial calcification. Methods Nicotine and vitamin D3 treated rats were studied. Vascular calcification was confirmed by using Von Kossa staining, measurement of calcium content,45Ca2+ uptake assay and alkaline phosphatase (ALP) activity. The plasma and vascular Ang Ⅱ and endothelin levels were measured by using radioimmunoassay. Angiotensinogen and endothelin mRNA levels were determined by RTPCR. Results The arterial calcium content, 45Ca2+ uptake and ALP activity were increased in calcification groups compared with control ( P ＜ 0.01 ). Administration of the angiotensin receptor antagonist losartan, the endothelin receptor antagonist bosentan, and the angiotensin-converting enzyme inhibitor captopril reduced significantly the arterial calcium content, 45Ca2+ uptake and ALP activity. In addition, the plasma and aortic Ang Ⅱ and endothelin contents, and vascular angiotensinogen and endothelin mRNA expression were significantly up-regulated ( P ＜0.05).Conclusions These findings suggest that functional renin-angiotensin system and endothelin pathway are involved in vascular calcification, and that activation of these systems could potentiate pathogenesis of arterial calcification. ( J Geriatr Cardiol 2004;1(2) :108-113. )

Aim To observe the influence of hydrogen sulfide on L-arginine/nitric oxide synthase(NOS)/NO pathway,explore the interaction between H_2S and NO as cardiovascular regulatory gasotransmitters.Methods Aortic thin slices in vitro were administrated with NaHS(10~(-7) mol?L~(-1)～10~(-4) mol?L~(-1)),a donor of H_2S,and incubated for 4 hours,or 50 ?mol?L~(-1) NaHS and incubated for 2 h,4 h and 6 h,respectively.The nitrite production Was measured with greiss assay;NOS activity and L-arginine transportation,with isotope tracer method;the eNOS and CAT1-A gene expression,with RT-PCR.Results After being given with NaHS(50 ?mol?L~(-1)) one time,and incubating for 2 h,the nitrite production decreased by 62%,NOS activity reduced by 48% and L-arginine transport decreased by 50%.After incubation for 6 h,the nitrite production further was inhibited by 19%(P0.05).NaHS(10~(-7) mol?L~(-1)～10~(-4) mol?L~(-1)) inhibited the L-arginine/NOS/NO pathway in a dose-dependent manner,and IC_(50) was 0.499,3.198 and 3.927 ?mol?L~(-1)(P