A survey shows Beijing has 295 000 overweight kids

Background Angiotensin Ⅱ （AngⅡ） and platelet-derived growth factor （PDGF）-BB can induce hypertrophy in the cultured rat cardiomyocytes through different signal transduction pathways. Angll stimulates growth through G protein coupled receptor （GPCR）, while PDGF-BB acts via receptor tyrosine kinase （RTK）. Although there has been much development on the individual Angll and PDGF-BB mediated signal pathways, little is known about the interactions between these two factors. Therefore, the crosstalk between Angll and PDGF-BB mediated signal pathways in the rat cardiomyocytes was investigated in this study.
Methods Primary culture of neonatal rat ventricular myocytes was prepared. The amount of tyrosine-phosphorylated and non-phosphorylated PDGF-β receptor, Goq/11, and phospholipase C （PLC） β3 were measured by immunoblotting analysis. The statistical analysis was done by one-way ANOVA.
Results Tyrosine-phosphorylated PDGF-β receptor was increased by 120.60% at 1 minute and recovered to the control level at 10 minutes after Angll stimulation. Phosphorylation of PDGF-β receptor triggered by Angll was blocked by Iosartan, a specific antagonist of AT1 receptor. PLC inhibitor U73122, protein kinase C （PKC） inhibitor staurosporine （STS） and mitogen-activated ERK activating kinase （MEK） inhibitor PD98059 also inhibited the Angll-induced phosphorylation of PDGF-β receptor. PDGF-BB slightly increased the expression of Gao/11 protein.
Conclusion Angll transactivates PDGF-β receptor via AT1 receptor-Gaq/11-PLC-PKC pathway in the rat cardiomyocytes. ERK also participates in the transactivation of PDGF-β receptor triggered by Angll.     

Effect of Sodium Tanshinone ⅡA Sulfonate on Phosphorylation of Extracellular Signal-regulated Kinasel/2 in Angiotensin Ⅱ-induced Hypertrophy of Myocardial Cells

Objective： To observe the effects of sodium tanshinone ⅡA sulfonate （STS） on angiotensin Ⅱ （Ang Ⅱ）-induced hypertrophy of myocardial cells through the expression of phosphorylated extracellular signal-regulated kinase （p-ERK1/2）. Methods： In the primary culture of neonatal rat myocardial cells, the total protein content in myocardial cells was determined by coomassie brilliant blue and the protein synthesis rate was measured by [3H]-Leucine incorporation as indexes for hypertrophy of myocardial cells. The expression of p-ERK1/2 was determined using Western blot and immunofluorescence labeling. Results： （1） The total protein and protein synthesis rate increased significantly in contrast to the control group after the myocardial cells were stimulated by Ang Ⅱ （1 μ mol/L） for 24 h; STS markedly inhibited the increment of the total protein level induced by Ang Ⅱ and the syntheses of protein. （2） After pretreatment of myocardial cells with Ang Ⅱ （1 μmol/L） for 5 min, the p-ERK1/2 protein expression was increased, with the most obvious effect shown at about 10 min; pretreatment of myocardial cells with STS at different doses （2, 10, 50μmol/L） for 30 min resulted in obvious inhibition of the expression of p-ERK1/2 stimulated by Ang Ⅱ in a dose-dependent manner. （3） After the myocardial cells were stimulated by AngⅡ （1 μ mol/L）, the immunofluorescence of ERK1/2 rapidly appeared in the nucleus. The activation and translocation process of ERK1/2 induced by Ang Ⅱ was blocked distinctly by STS. （Conclusion： STS inhibited the myocardial cell hypertrophy induced by Ang Ⅱ, and the mechanism may be associated with the inhibition of p-ERK1/2 expression.     

Nardosinone protects H9c2 cardiac cells from angiotensin II-induced hypertrophy

Pathological cardiac hypertrophy induced by angiotensin Ⅱ （Ang Ⅱ ） can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the roots ofNardostachys chinensis, a well-known traditional Chinese medicine. In order to investigate the effects of nardosinone on Ang Ⅱ-induced cardiac cell hypertrophy and the related mechanisms, the myoblast cell line H9c2, derived from embryonic rat heart, was treated with nardosi- none （25, 50, 100, and 200μmol/L） or Ang Ⅱ （1 μmol/L）. Then cell surface area and mRNA expression of classical markers of hypertrophy were detected. The related protein levels in PI3K/Akt/mTOR and MEK/ERK signaling pathways were examined by Western blotting. It was found that pretreatment with nardosinone could significantly inhibit the enlargement of cell surface area induced by Ang Ⅱ. The mRNA expression of ANP, BNP and 13-MHC was obviously elevated in Ang Ⅱ-treated H9c2 cells, which could be effectively blocked by nardosinone at the concentration of 100μmol/L. Further study revealed that the protective effects of nardosinone might be mediated by repressing the phosphorylation of related proteins in PI3K/Akt and MEK/ERK signaling pathways. It was suggested that the inhibitory effect of nardosinone on Ang Ⅱ-induced hypertrophy in H9c2 cells might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways.     

Effect of Atorvastatin on Expression of Peroxisome Proliferator-activated Receptor Beta/delta in AngiotensinⅡ-induced Hypertrophic Myocardial CellsIn Vitro

Objective To explore the effect of atorvastatin on cardiac hypertrophy and to determine the potential mechanism involved. Methods Anin vitro cardiomyocyte hypertrophy from neonatal rats was induced with angiotensinⅡ (AngⅡ) stimulation. Before AngⅡ stimulation, the cultured rat cardiac myocytes were pretreated with atorvastatin at different concentrations (0.1, 1, and 10μmol/L). The following parameters were evaluated: the myocyte surface area,3H-leucine incorporation into myocytes, mRNA expressions of atrial natriuretic peptide, brain natriuretic peptide, matrix metalloproteinase 9, matrix metalloproteinase 2, and interleukin-1β, mRNA and protein expressions of theδ/β peroxisome proliferator-activated receptor (PPAR) subtypes. Results It was shown that atorvastatin could ameliorate AngⅡ-induced neonatal cardiomyocyte hypertrophy in the area of cardiomyocytes,3H-leucine incorporation, and the expression of atrial natriuretic peptide and brain natriuretic peptide markedly. Meanwhile, atorvastatin also inhibited the augmented mRNA level of several cytokines in hypertrophic myocytes. Furthermore, the down-regulated expression of PPAR-δ/β at both the mRNA and protein levels in hypertrophic myocytes could be significantly reversed by atorvastatin treatment. Conclusions Atorvastatin could improve AngⅡ-induced cardiac hypertrophy and inhibit the expression of cytokines. Such effect might be partly achieved through activation of the PPAR-δ/β pathway.     

Effect of irbesartan on angiotensin Ⅱ-induced hypertrophy of human proximal tubular cells

Background Intrarenal activation of the renin angiotensin system (RAS) plays an important role in mediating renal fibrosis. Both angiotensin converting enzyme inhibitors (ACEIs) and angiotensin Ⅱ (AngⅡ) receptor antagonists have been shown to exert a protective role against diabetic and non-diabetic nephropathy. However, the exact mechanism of how blocking local RAS prevents renal fibrosis is unclear. The present study was to investigate the influence of a new AngⅡ receptor antagonist, irbesartan (Irb), on AngⅡ-induced hypertrophy in human proximal tubular cell line (HK-2). Methods The cell line, HK-2, was grown in Dulbeccos’s Modified Eagle’s Medium containing 10% heat-inactivated fetal calf serum. After rested in serum-free medium for 24 hours, the effects of Irb on AngⅡ (10(-7) mol/L)-induced ［3H］-leucine incorporation, total protein content (measured by the Coomassie brilliant blue G250 method), and change in cell size (determined by scanning electron microscopy) were observed. The influence of Irb on the cell cycle was analyzed by fluorescence activated cell sorter (FACS) flow cytometry. Results AngⅡ induced cell hypertrophy in a time and dose dependent manner. Stimulation of cells with AngⅡ for 48 hours resulted in a increase in ［3H］-leucine incorporation ［0 hour: (5584±1016) cpm/10(5)cells vs 48 hours: (10741±802) cpm/10(5)cells, P<0.05］, which was significantly attenuated by treatment with Irb. AngⅡ significantly increased the total protein content in HK-2 cells ［control: (0.169±0.011) mg/10(5)cells vs AngⅡ group: (0.202±0.010) mg/10(5) cells, P<0.05］, which was also markedly inhibited by cotreatment with Irb (P<0.01). Scanning electron microscopy showed that AngⅡ induced an increase in average physical cell size, which was significantly inhibited by Irb ［control: (11.92±1.62) μm; AngⅡ group: (20.63±3.83) μm; AngⅡ+Irb group: (13.59±3.15) μm; P<0.01 vs control, respectively］. Furthermore, flow cytometry revealed that AngⅡ arrested cells in the G0-G1 phase, which was significantly reversed by treatment with Irb ［G0-G1 cells in AngⅡ group: (76.09±1.82)%, in AngⅡ+Irb group: (67.00±2.52)%, P<0.05］.Conclusion Irb can inhibit AngⅡ-induced hypertrophy in HK-2 cells.     

Effects of Cyclosporine A on Angiotensin Ⅱ-induced Cardiomyocyte Hypertrophy in Neonatal Rats

Summary： The effects of cyclosporine A （CsA） on Angiontensin Ⅱ （Ang Ⅱ ）-induced protein contents, c los protein levels and cytosolic Ca^2＋ level （[Ca^2＋]i） in cultured eardiomyocytes of neonatal rats were observed. Total protein contents were determined by Bradford method. The expression of c-fos protein was detected by Western blot. （[Ca^2＋]i） labeled with fluorescent probe Fluo-3/AM was measured under a laser scanning confoeal microscope. The results revealed that as compared with control, the total protein contents were increased in cardiomyocytes treated with Ang Ⅱ （10-1 mol/ L）, which could be inhibited by CsA in a dose-dependent manner. It was found that Ang Ⅱ could increase the c-los protein expression, which could be inhibited by CsA in a dose-dependent manner. Ang Ⅱ induced the [Ca^2＋]i elevation in cardiomyocytes. CsA did not influence the resting intracellular Ca^2＋ , but inhibited significantly the Ang Ⅱ-induced [Ca^2＋]i elevation. It was concluded that CsA can suppress the Ang Ⅱ-induced c-fos protein expression and [Ca^2＋]i elevation in single cardiomyocyte, which might play a role in the prevention of Ang Ⅱ-induced cardiomyocyte hypertrophy by CsA.     

Effects of transforming growth factor-β1 and signal protein Smad3 on rat cardiomyocyte hypertrophy

Background SMAD proteins have recently been identified as the first family of putative transforming growth factor-β1 (TGF-β1) signal transducers. This study was to investigate the effects of TGF-β1 and signal protein Smad3 on rat cardiac hypertrophy.Methods The incorporation of [3H]-leucine was measured to determine the hypertrophy of cardiomyocyte incubated with different doses of TGF-β1 in cultured neonatal cardiomyocytes. The model of rat cardiac hypertrophy was produced with constriction of the abdominal aorta. At different times after the operation, rats were killed, and their left ventricular mass index (LVMI) determined.The mRNA expression of TGF-β1 and Smad3 of cultured cells and hypertrophic left ventricles were assessed by RT-PCR. The protein expression of Smad3 was assessed by Western blot.Results In cultured neonatal cardiomyocytes, TGF-β1 significantly promoted incorporation of [3H]-leucine. With the concentration of 3 pg/L, it increased the expression of Smad3 in mRNA and protein levels after 15 minutes, and continued for up to 8 hours of cultured cardiomyocytes. The LVMI and theexpression of TGF-β1 (mRNA) and Smad3 (mRNA and protein) of hypertrophic left ventricle were increased by day 3 after the operation and continued to the 4th week. The peak expression of these was in the second week after operation.Conclusion TGF-β1 has positive effects on could be related to the pathologic progressionrat cardiomyocyte hypertrophy. Signal protein Smad3 of rat cardiac hypertrophy.     

Effect of Sodium Tanshinone Ⅱ A Sulfonate on Phosphorylation of Extracellular Signal-regulated Kinase1/2 in Angiotensin Ⅱ-induced Hypertrophy of Myocardial Cells

Objective:To observe the effects of sodium tanshinone Ⅱ A sulfonate(STS)on angiotensin Ⅱ(Ang Ⅱ)-induced hypertrophy of myocardial cells through the expression of phosphorylated extracellular signal-regulated kinase(P-ERK1/2).Methods:In the primary culture of neonatal rat myocardial cells.the total protein content in myocardial cells was determined by coomassie brilliant blue and the protein synthesis rate was measured by[3H]-Leucine incorporation as indexes for hypertrophy of myocardial cells.The expression of p-ERK1/2 was determined using Western blot and immunofluorescence Iabeling.Results:(1)The totaI protein and protein synthesis rate increased significantly in contrast to the control group after the myocardial cells were stimulated by Ang Ⅱ (1 μmol/L)for 24 h;STS markedly inhibited the increment of the total protein level induced by Ang Ⅱ and the syntheses of protein.(2)After pretreatment of myocardial cells with Ang Ⅱ(1 μ mol/L)for 5 min,the p-ERK1/2 protein expression was increased,with the most obvious effect shown at about 10 min;pretreatment of myocardial cells with STS at different doses(2,10,50 μ mol/L)for 30 min resulted in obvious inhibition of the expression of p-ERK1/2 stimulated by Ang Ⅱ in a dose-dependent manner.(3)After the myocardial cells were stimulated by Ang Ⅱ(1 μ mol/L),the immunofluorescence of ERK1/2 rapidly appeared in the nucleus.The activation and translocation process of ERK1/2 induced by Ang Ⅱ was blocked distinctly by STS.Conclusion:STS inhibited the myocardial cell hypertrophy induced by Ang Ⅱ,and the mechanism may be associated with the inhibition of p-ERK1/2 expression.     

A combination of Ang Ⅱ and carbon tetrachloride acce lerates process of hepatic fibrosis

Objective To assess whether Angiotensin Ⅱ（Ang Ⅱ）and carbon tetrachloride(CCl4) used in combination could accelerate the process of fibrosis and whether Ang Ⅱ play a role in exaggerating hepatic fibrosis in rats.Methods Ang Ⅱ was injected into the abdominal cavity of Sprague-Dawley(SD) rats together with subcutaneous injection of CCl2.Rats were killed after 14 and 28d.Blood serum and liver specimen were collected.The extent of fibrosis in the stained liver tissue sections was determined with the KS 400 Image Analysis System.Results Rats receiving Ang Ⅱ and CCl4 for 28d showed extensive liver fibrosis.Along with the increase of hepatic fibrosis,the serum concentration of Ang Ⅱ went up gradually.Conclusions A combination of AngⅡ and CCl4 would accelerate the process of hepatic fibrosis.AogⅡ probably took part in the occurrence of heparic fibrosis.     

Effect of angiotensin Ⅱ and angiotensin Ⅱ type 1 receptor antagonist on the proliferation,contraction and collagen synthesis in rat hepatic stellate cells

Background Angiotensin Ⅱ （Ang Ⅱ） is a very important vasoactive peptide that acts upon hepatic stellate cells （HSCs）, which are major effector cells in hepatic cirrhosis and portal hypertension. The present study was aimed to investigate the effects of Ang Ⅱ and angiotensin Ⅱ type 1 receptor antagonist （AT1RA） on the proliferation, contraction and collagen synthesis in HSCs.
Methods HSC-T6 rat hepatic stellate cell line was studied. The proliferation of the HSC cells was evaluated by MTT colorimetric assay while HSC DNA synthesis was measured by ^3H-thymidine incorporation. The effects of angiotensin Ⅱ and AT1RA on HSCs contraction were studied by analysis of the contraction of the collagen lattice. Cell culture media were analyzed by RT-PCR to detect secretion of collagen Ⅰ （Col Ⅰ）, collagen Ⅲ （Col Ⅲ） and transforming growth factor β1 （TGF-β1） by enzyme linked immunosorbent assay. HSC was harvested to measure collagen Ⅰ, collagen Ⅲ and tissue inhibitor of metalloproteinase-1 （TIMP-1） mRNA expression.
Results Ang Ⅱ （（1×10^-10-1×10^-4）mol/L）stimulated DNA synthesis and proliferation in HSCs compared with untreated control cells. AT1RA inhibited angiotensin Ⅱ induced proliferation of HSCs. A linear increase in the contractive area of collagen lattice correlated with the concentration of angiotensin Ⅱ （1×10^-9-1×10^-5 mol/L） and with time over 48 hours. AT1RA blocks angiotensin Ⅱ induced contraction of collagen lattice. Col Ⅰ, Col Ⅲ and TGF-β1 levels of the Ang Ⅱ group were higher than those of control group and this increase was downregulated by AT1RA. The mRNA expressions of Col Ⅰ, Col Ⅲ and TIMP-1 were higher in HSCs from the Ang Ⅱ group than the control group and downregulated by AT1RA.
Conclusions Angiotensin Ⅱ increased DNA synthesis and proliferation of HSCs in a dose-dependent manner, stimulated the contraction of HSCs dose- and time-dependently. Angiotensin also promoted excretion of Col I, Col Ⅲ and TGF-β1 lev     

结缔组织生长因子在血管紧张素Ⅱ诱导的人近端肾小管上皮细胞肥大中的作用

目的　探讨结缔组织生长因子 (CTGF)在介导血管紧张素Ⅱ (AngⅡ )诱导的人肾近端小管细胞肥大中的作用。方法　用 [3 H] 亮氨酸掺入、考马斯亮蓝蛋白质定量技术分别观察抗CTGF抗体对AngⅡ诱导的人肾近端小管上皮细胞株 (HK 2 )细胞内蛋白质从头合成及细胞内蛋白质含量的影响 ;用流式细胞分析技术观察抗CTGF抗体对AngⅡ诱导的细胞周期分布改变的影响 ;用扫描电镜技术观察抗CTGF抗体对AngⅡ诱导细胞形态变化的影响。 结果　AngⅡ可以显著诱导细胞内[3 H] 亮氨酸掺入和细胞内总蛋白质含量增加的作用 ,呈浓度和时间依赖性 ;抗CTGF抗体对AngⅡ诱导的细胞内总蛋白质含量、[3 H] 亮氨酸掺入量的增加有抑制作用 ,呈浓度和时间依赖性。AngⅡ作用于细胞 4 8h后 ,细胞平均直径、G0 G1期细胞百分比显著增加 (均P <0 0 1) ,抗CTGF抗体可显著抑制AngⅡ诱导的细胞直径增加和细胞周期阻滞 (均P <0 0 5或P <0 0 1)。结论　AngⅡ可以诱导肾小管上皮细胞发生肥大 ,CTGF可能介导了AngⅡ诱导的肾小管上皮细胞肥大效应。     

ROLE OF CALCINEURIN IN ANGIOTENSIN II INDUCED CARDIAC MYOCYTE HYPERTROPHY OF RATS

Objective. The present study investigated the role of calcineurin in angiotensin II(AngII) induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII treated cardiomyocytes was tested by using PNPP;protein synethsis rate was assessed by 3H leucine incorporation; atrial natriuretic factor(ANF) Mrna level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase(LDH) levels in cultured medium and by dyed cell numbers. Result. After stimulation of 10,100 and 1 000nmol/L of AngII, calcineurin activities in the cardiomyocytes were increased by 13％ ,57％ (P< 0.05) and 228％ (P< 0.01) respectively, compared with control group. Cyclosporin A(CsA), a specific inhibitor of calcineurin, markedly inhibited the calcineurin activity and decreased the 3H leucine incorporation in AngII treated cardiomyocytes in a dose dependent manner. It was also found that CsA slightly reduced the Mrna level of ANF gene in AngII stimulated cardiomyocytes. Conclusion. During AngII induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII induced myocardial hypertrophy of rats.     

磷脂酶C在血管紧张素II诱导心肌细胞血小板衍生 生长因子受体表达中的作用

目的　探讨磷脂酶C在血管紧张素II(AngII)诱导心肌细胞血小板衍生生长因子受体 - β(PDGF - β)表达中的作用。 方法　分离纯化培养的乳鼠心肌细胞 ,以 10 -7mol·L-1AngII刺激为AngII组 ,以 10 -5mol·L-1U73 12 2 (一种特异性磷脂酶C抑制剂 )预孵育 3 0min为U73 12 2组 ,以正常的乳鼠心肌细胞为对照组 ,免疫印迹法测定培养 6h时心肌细胞PDGF- β受体的含量。 结果　AngII刺激培养 6h的乳鼠心肌细胞PDGF - β受体表达增强 (P <0 .0 5 ) ,U73 12 2可部分抑制AngII对PDGF - β受体表达的诱导作用。 结论　磷脂酶C参与AngII上调心肌细胞PDGF - β受体表达的信号转导途径     

ERK1/2介导去甲肾上腺素对内皮祖细胞的功能调节

目的：探讨去甲肾上腺素（NE）对内皮祖细胞（EPCs）增殖和迁移能力的调节作用及其分子机制。 方法:将培养的健康成人外周血EPCs用不同浓度的NE、肾上腺受体拮抗剂或者MAPK信号通道阻滞剂干预,检测内皮祖细胞的增殖和迁移能力,以及Erk 1/2信号通路的激活情况。结果:NE浓度依赖性地促进EPCs的增殖能力（相对于对照组,0.01μM组EPCs增加48.3±23.3%,0.1μM组增加了70.5±35.6%、1μM组增加了82.4±14.9%,10μM组增加了100.3±48.1%,100μM组增加了53.6±16.5%）。α受体拮抗剂酚妥拉明（43.1±7.3% VS 48.5±9.0%）、选择性β2肾上腺受体拮抗剂I127（32.9±4.4% VS 29.3±5.8%）和ERK1/2 抑制剂A6355（-14.4±3.2% VS-9.0±11.4%）能够阻断NE的刺激效应,而β1受体拮抗剂美托洛尔（64.0±9.1% VS 109.6±7.0%, p < 0.05）、JNK抑制剂SP600125（-24.3±9.7% VS 48.6±40.7%, p < 0.05）和p38抑制剂PD169318（-1.5±9.8% VS 73.8±21.8%, p < 0.05）不能阻断。NE10μM显著促进EPCs的迁移（124.1±12.2 / 高倍视野 VS 71.7±19.6 / 高倍视野, p < 0.05）,酚妥拉明10μM（57.2±14.3 / 高倍视野）和I127 10μ（61.3±11.5 / 高倍视野）能够阻断这种作用,而美托洛尔10μM（112.8±26.0 / 高倍视野）不能。NE能够浓度依赖性地激活EPCs 内的Erk 1/2,而酚妥拉明和I127能够阻断Erk 1/2激活,而美托洛尔不能。结论：NE通过α和β2肾上腺受体激活Erk 1/2促进EPCs的迁移和增殖。     

卡维地洛对病毒性心肌炎小鼠ERK1/2通路的影响

目的 观察卡维地洛对病毒性心肌炎小鼠心肌组织细胞外信号调节激酶（ERK1/2）信号通路的影响并探讨其可能的作用机制.方法 188只清洁级近交系4~6周龄雄性Balb/C小鼠随机分成4组.心肌炎对照组（C组）、美托洛尔干预组（M组）、卡维地洛干预组（K组）各60只,空白对照组（B组）8只做总体对照.观察各组小鼠各时间点（1、3、7和14d）的心肌组织病理学改变、血清cTnI水平、IL1β含量及心肌组织磷酸化ERK1/2含量的动态变化.结果 病程第1、3天,M组、K组心肌磷酸化ERK1/2水平低于C组（P＜0.01）,病程第14天,K组心肌磷酸化ERK1/2水平仍低于C组（P＜0.01）.病程第3、7天,M组、K组心肌组织炎症积分、血清cTnI和IL-1β水平低于C组（P＜0.05或0.01）,且K组上述水平下降更加显著（P＜0.01）.结论 卡维地洛可能通过β1、β2肾上腺素能受体双重阻滞作用,抑制ERK1/2信号通路活化,减轻病毒性心肌炎引起的心肌损伤.     

细胞外信号调节激酶1/2在心血管系统疾病中的作用

丝裂原活化蛋白激酶(MAPK)信号转导通路是细胞内的重要信息传递系统,细胞外信号调节激酶1/2(ERK1/2)作为MAPK家族的重要组成部分,是将信号从细胞表面受体转导至细胞核的关键。ERK1/2磷酸化参与了心肌细胞肥厚、凋亡的过程以及血管平滑肌细胞增殖等多种生物学反应。然而,对于ERK1/2在心血管系统疾病发生、发展过程中所起的作用仍有争议,且未阐明在具体的病理生理过程中其上游激活物及下游作用靶点。