Search PubMed⌕ Search

Biomedical subjects

P Anversa

Publications and source records attributed to P Anversa.

At least 37 records · Page 2Linked to original sources
PubMed2000

Inhibition of p53 function prevents renin-angiotensin system activation and stretch-mediated myocyte apoptosis.

To determine whether stretch-induced activation of p53 is necessary for the up-regulation of the local renin-angiotensin system and angiotensin II (Ang II)-induced apoptosis, ventricular myocytes were infected with an adenoviral vector carrying mutated p53, Adp53m, before 12 hours of stretch. Noninfected myocytes and myocytes infected with AdLacZ served as controls. Stretching of Adp53m-infected myocytes prevented stimulation of p53 function that conditioned the expression of p53-dependent genes; quantity of angiotensinogen (Aogen), AT(1), and Bax decreased, whereas Bcl-2 increased. Ang II generation was not enhanced by stretch. Conversely, stretch produced opposite changes in noninfected and AdLacZ-infected myocytes: Aogen increased twofold, AT(1) increased 2. 1-fold, Bax increased 2.5-fold, and Ang II increased 2.4-fold. These responses were coupled with 4.5-fold up-regulation of wild-type p53. Stretch elicited comparable adaptations in p53-independent genes, in the presence or absence of mutated p53; renin increased threefold, angiotensin-converting enzyme increased ninefold, and AT(2) increased 1.7-fold. Infection with Adp53m inhibited myocyte apoptosis after stretch. Conversely, stretch increased apoptosis by 6.2-fold in myocytes with elevated endogenous wild-type p53. Thus, a competitor of p53 function interfered with both stretch-induced Ang II formation and apoptosis, indicating that p53 is a major modulator of myocyte renin-angiotensin system and cell survival after mechanical deformation.

Angiotensin II↗
PubMed2000

Telomere shortening is an in vivo marker of myocyte replication and aging.

To determine whether adult cardiac myocytes are capable of multiple divisions and whether this form of growth is restricted to a subpopulation of cells that retain this capacity with age, telomere lengths were measured in myocyte nuclei isolated from the left ventricle of fetal and neonatal Fischer 344 rats and rats at 4, 12, and 27 months after birth. Two independent methodologies were used for this analysis: laser scanning cytometer and confocal microscopy. In each case, fluorescence intensity of a peptide nucleic acid probe specific for telomeric sequence was evaluated. The two techniques yielded comparable results. Telomeric shortening increased with age in a subgroup of myocytes that constituted 16% of the entire cell population. In the remaining nondividing cells, progressive accumulation of a senescent associated nuclear protein, p16(INK4), was evidenced. In conclusion, a significant fraction of myocytes divides repeatedly from birth to senescence, counteracting the continuous death of cells in the aging mammalian rat heart.

Aging↗
PubMed2000

Up-regulation of AT(1) and AT(2) receptors in postinfarcted hypertrophied myocytes and stretch-mediated apoptotic cell death.

To determine whether up-regulation of AT(1) and AT(2) receptors occurred in hypertrophied myocytes after infarction and whether AT(2) played a role in stretch-mediated apoptosis, left ventricular myocytes were dissociated from the surviving portion of the wall 8 days after coronary occlusion and cardiac failure in rats. Control cells were obtained from sham-operated animals. Myocytes were stretched in an equibiaxial stretch apparatus and angiotensin II (Ang II) formation and cell death were measured 3 and 12 hours later. AT(1) and AT(2) proteins were evaluated in freshly isolated myocytes and after stretch. The effects of AT(1) and AT(2) antagonists on stretch-induced Ang II synthesis and apoptosis were also established. Myocardial infarction increased AT(1) and AT(2) in myocytes and stretch further up-regulated these receptors. Ang II levels were higher in postinfarcted myocytes and this peptide increased with the duration of stretch in both groups of cells. Similarly, apoptosis increased with time in control and postinfarcted myocytes. Absolute values of Ang II and apoptosis were greater in myocytes from infarcted hearts at 3 and 12 hours after stretch. Addition of AT(1) blocker to cultures inhibited stretch-activated apoptosis in both myocyte populations as well as the generation of Ang II in postinfarcted myocytes. In contrast, AT(2) antagonists had no impact on these cellular events. In conclusion, Ang II stimulated cell death through AT(1) receptor activation, whereas ligand binding to AT(2) receptor did not alter Ang II concentration and apoptosis in normal and postinfarcted hypertrophied myocytes.

Angiotensin II↗
PubMed2000

Ischemic cardiomyopathy and the cellular renin-angiotensin system.

BACKGROUND: Ischemic cardiomyopathy produced by non-occlusive coronary artery constriction is characterized by left ventricular failure and right ventricular dysfunction, but whether the local renin-angiotensin system (RAS) is implicated in myocyte dysfunction and cell death remains unclear. METHODS: Changes in single-cell mechanics, the localization of the various constituents of RAS in the myocardium, and the effects of angiotensin II (Ang II) stimulation on myocyte performance and cell death were measured. RESULTS: Chronic ischemia is coupled with alterations in the mechanical properties and calcium (Ca2+) transients of the remaining viable myocytes. The abnormalities in myocyte mechanics consist of depression in peak shortening and velocity of shortening. Moreover, peak systolic Ca2+ is significantly decreased in the cells. In vitro stimulation with Ang II ameliorates myocyte function and systolic Ca2+. Additionally, adult myocytes express genes for renin, angiotensinogen, angiotensin-converting enzyme (ACE), and Ang II receptors. Renin, ACE, and Ang II receptors mRNAs increase under the setting of impaired coronary perfusion. Similarly, the percentage of myocytes containing renin, Ang I, and Ang II increases as well. In vitro studies of neonatal and adult ventricular myocytes indicate that Ang II triggers programmed myocyte cell death and this phenomenon is mediated by activation of the AT1 receptor sub-type. Importantly, the AT1-receptor blocker, losartan, completely inhibits apoptosis. CONCLUSIONS: These multiple observations are consistent with the notion that Ang II may exert 3 separate functions on the heart: (1) stimulation of myocyte hypertrophy, (2) amelioration of myocyte contractile performance, and (3) activation of the suicide program of myocytes.

Angiotensin II↗
PubMed2000

Myocyte death in streptozotocin-induced diabetes in rats in angiotensin II- dependent.

To determine whether myocyte death and angiotensin II (AT II) formation are implicated in the development of diabetic cardiomyopathy, rats were injected with streptozotocin, and apoptosis and necrosis were measured at 3, 10, and 28 days. Expression of the components of the renin-angiotensin system (RAS) and AT II levels were assessed at 3 days. The percentage of AT II-labeled myocytes and the number and distribution of AT II sites in myocytes were measured at 3 and 10 days. The effects of AT1 blockade on local RAS and cell death were examined at 3 days. Diabetes was characterized by myocyte apoptosis that peaked at 3 days and decreased at 10 and 28 days, in spite of high concentrations of blood glucose. Cell necrosis was absent throughout. Angiotensinogen, renin, and AT1 receptor increased in myocytes from diabetic rat hearts, while angiotensin-converting enzyme and AT2 remained constant. AT II quantity increased severalfold, as did the fraction of AT II positive cells and the number of AT II sites per myocyte. However, AT II labeling decreased at 10 days, which paralleled the reduction in myocyte death. AT1 antagonist inhibited upregulation of this receptor and angiotensinogen, which prevented AT II synthesis and myocyte death at their peaks with diabetes. An aggregate 30% myocyte loss and a 14% increase in the volume of viable cells were found in diabetic rats at 28 days. Thus diabetic cardiomyopathy may be viewed as an AT II-dependent process in which that peptide plays a critical role in myocyte death and hypertrophy.

Angiotensin II↗
PubMed2000

Plasticity of the pathologic heart.

This review addresses two relevant issues concerning the adaptation of the failing heart: myocyte growth and myocyte death. Recent results are summarized to support the notion that adult ventricular myocytes are not terminally differentiated cells and myocyte replication occurs in the normal heart and is potentiated by overloads. On this basis, myocyte hypertrophy and proliferation both contribute to the remodeling of the pathologic heart in animals and humans. Additionally, the controversy regarding the activation of apoptosis in the stressed myocardium is emphasized and published results are discussed. Available information demonstrates unequivocally that cell death by this mechanism takes place in the diseased heart and may have significant implications in the progression of ventricular dysfunction to end-stage failure. The importance of recognizing that electron microscopy is inappropriate for the identification and quantification of myocyte apoptosis is strongly indicated. Moreover, myocyte necrosis is presented as a relevant component of the decompensated heart. In summary, the dogma that myocytes cannot reenter the cell cycle and undergo mitotic division is proven to be obsolete and invalid. Similarly, the dogma that myocytes can die only by necrosis is contrary to any objective interpretation of published findings. Myocyte necrosis and apoptosis, and myocyte hypertrophy and proliferation are major elements of the plasticity of the heart.

Adaptation, Physiological↗
PubMed1999

Myocyte death in the failing human heart is gender dependent.

Cardiovascular disease is delayed and less common in women than in men. Myocyte death occurs in heart failure, but only apoptosis has been documented; the role of myocyte necrosis is unknown. Therefore, we tested whether necrosis is as important as apoptosis and whether myocyte death is lower in women than in men with heart failure. Molecular probes were used to measure the magnitude of myocyte necrosis and apoptosis in 7 women and 12 men undergoing transplantation for cardiac failure. Myocyte necrosis was evaluated by detection of DNA damage with blunt end fragments, whereas apoptosis was assessed by the identification of double-strand DNA cleavage with single base or longer 3' overhangs. An identical analysis of these forms of cell death was performed in control myocardium. Heart failure showed levels of myocyte necrosis 7-fold greater than apoptosis in patients of both sexes. However, cell death was 2-fold higher in men than in women. Heart failure resulted in a 13-fold and 27-fold increase in necrosis in women and men, respectively. Apoptosis increased 35-fold in women and 85-fold in men. The differences in cell death between women and men were confirmed by the electrophoretic pattern of DNA diffusion and laddering of isolated myocytes. The lower degree of cell death in women was associated with a longer duration of the myopathy, a later onset of cardiac decompensation, and a longer interval between heart failure and transplantation. In conclusion, myocyte necrosis and apoptosis affect the decompensated human heart; each contributes to the evolution of cardiac failure. However, the female heart is protected, at least in part, from necrotic and apoptotic death signals.

Apoptosis↗
PubMed1999

Insulin-like growth factor-1 attenuates the detrimental impact of nonocclusive coronary artery constriction on the heart.

Coronary artery narrowing (CAN) induces tissue injury, which may involve myocyte necrosis and apoptosis. Insulin-like growth factor (IGF)-1 may counteract cell death, modifying the detrimental effects of myocardial ischemia. On this basis, CAN was produced in female FVB.Igf+/- mice and nontransgenic littermates, and the animals were euthanized 7 days later. CAN consisted of an 82% reduction in the vessel luminal cross-sectional area in both groups of mice. Severe left ventricular dysfunction was present in CAN nontransgenic and transgenic mice, but heart and left ventricular weights increased more in littermates than in FVB.Igf+/- mice. Similarly, the changes in chamber volume and diastolic wall stress were greater in nontransgenic mice. Subacute tissue injury, represented by foci of replacement fibrosis, was 2.6-fold higher in CAN littermates than in FVB.Igf+/- mice. Ongoing myocyte necrosis was 5-fold greater in nontransgenic mice, whereas apoptosis was low and did not differ in the 2 groups of mice. In CAN nontransgenic mice, myocyte necrosis was 12-fold more frequent than apoptosis but, in CAN transgenic mice, these 2 types of cell death were comparable. alpha-Myosin and beta-myosin isoform mRNAs were affected by CAN, but alpha-myosin mRNA was reduced more in nontransgenic mice. In conclusion, myocyte necrosis and replacement fibrosis are the prevailing forms of myocardial damage induced by CAN. Constitutive overexpression of IGF-1 attenuates myocyte necrosis and tissue injury, having no effect on cell apoptosis. These factors limit ventricular dilation, myocardial loading, cardiac hypertrophy, and alterations in alpha- and beta-myosin isoform expression.

Animals↗
PubMed1999

Overexpression of insulin-like growth factor-1 attenuates the myocyte renin-angiotensin system in transgenic mice.

Constitutive overexpression of insulin-like growth factor-1 (IGF-1) in myocytes protects them from apoptosis and interferes with myocyte hypertrophy in the normal and pathological heart. Conversely, angiotensin II (Ang II) triggers cell death and promotes myocyte hypertrophy. Moreover, activation of p53 upregulates the cellular renin-angiotensin system (RAS). Therefore, IGF-1 overexpression in FVB.Igf+/- mice may downregulate the local RAS through the attenuation of p53 and p53-inducible genes. On this basis, p53 DNA binding activity to angiotensinogen (Aogen), bax, and the AT1 receptor was determined in left ventricular myocytes from FVB.Igf-/- and FVB.Igf+/- mice. The quantity of Bax, Bcl-2, Aogen, and AT1 receptor in these cells was evaluated. The presence of Mdm2-p53 complexes was also established. Finally, Ang II levels in myocytes were measured. Upregulation of IGF-1 in myocytes was associated with a protein-to-protein interaction between Mdm2 and p53, which attenuated p53 transcriptional activity for bax, Aogen, and AT1 receptor. Similarly, the amount of Bax, Aogen, and AT1 receptor proteins in these cells decreased. In contrast, the expression of Bcl-2 remained constant. The downregulation of Aogen in myocytes from FVB.Igf+/- mice was characterized by a reduction in Ang II. In conclusion, IGF-1 negatively influences the myocyte RAS through the upregulation of Mdm2 and its binding to p53. This may represent the molecular mechanism responsible for the effects of IGF-1 on cell viability and myocyte hypertrophy in the nonpathological and pathological heart in vivo.

Angiotensin II↗
PubMed1999

Cell death in acromegalic cardiomyopathy.

BACKGROUND: Prolonged untreated acromegaly leads to a nonspecific myopathy characterized by ventricular dysfunction and failure. However, the mechanisms responsible for the alterations of cardiac pump function remain to be defined. Because cell death is implicated in most cardiac disease processes, the possibility has been raised that myocyte apoptosis may occur in the acromegalic heart, contributing to the deterioration of ventricular hemodynamics. METHODS AND RESULTS: Ten acromegalic patients with diastolic dysfunction and 4 also with systolic dysfunction were subjected to electrocardiography, Holter monitoring, 2-dimensional echocardiography, cardiac catheterization, and biventricular and coronary angiography before surgical removal of a growth hormone-secreting pituitary adenoma. Endomyocardial biopsies were obtained and analyzed quantitatively in terms of tissue scarring and myocyte and nonmyocyte apoptosis. Myocardial samples from papillary muscles of patients who underwent valve replacement for mitral stenosis were used for comparison. The presence of apoptosis in myocytes and interstitial cells was determined by confocal microscopy with the use of 2 histochemical methods, consisting of terminal deoxynucleotidyl transferase (TdT) assay and Taq probe in situ ligation. Acromegaly was characterized by a 495-fold and 305-fold increase in apoptosis of myocytes and nonmyocytes, respectively. The magnitude of myocyte apoptosis correlated with the extent of impairment in ejection fraction and the duration of the disease. A similar correlation was found with the magnitude of collagen accumulation, indicative of previous myocyte necrosis. Myocyte death was independent from the hormonal levels of growth hormone and insulin-like growth factor-1. Apoptosis of interstitial cells did not correlate with ejection fraction. CONCLUSIONS: Myocyte cell death, apoptotic and necrotic in nature, may be critical for the development of ventricular dysfunction and its progression to cardiac failure with acromegaly.

Acromegaly↗
PubMed1999

Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart.

Most patients with severe coronary artery disease have normal baseline myocardial blood flow. Therefore, interventions aimed at inducing therapeutic angiogenesis in these patients should cause new blood vessel growth in the heart in the absence of chronic ischemia. It was examined whether adenovirus-mediated gene transfer of recombinant, secreted acidic fibroblast growth factor (sp+aFGF(1-154)), next to a major epicardial artery, may induce neovascularization and reduce the risk region for myocardial infarction upon coronary ligation near the injection site. Fifteen days prior to coronary artery occlusion, rabbits were treated with intramyocardial injections of AdCMV.sp+aFGF(1-154), the control vector AdCMV.NLSbetagal (1 x 10(9) plaque-forming units), or saline. Messenger RNA transcripts for aFGF(1-154) were present up to 12 days after injection in the tissues exposed to AdCMV.aFGF(1-154). Following coronary artery occlusion rabbits treated with AdCMV. sp+aFGF(1-154) showed a 50% reduction of the risk region for myocardial infarction (P < 0.01 vs control). Histologic analysis showed a twofold increase in length density of intramural coronary arterioles (P < 0.01 vs control) and a 17% increase in length density of the capillary network (P < 0.001) in the myocardium exposed to AdCMV.sp+aFGF(1-154). Thus, gene therapy with AdCMV. sp+aFGF(1-154) can induce angiogenesis in the absence of chronic ischemia. The newly formed collateral blood vessels provide an anatomical basis for the reduction in the risk region for myocardial infarction upon subsequent occlusion of the coronary artery in proximity of the site where angiogenesis was induced.

Adenoviridae↗
PubMed1999

Insulin-like growth factor-1 induces Mdm2 and down-regulates p53, attenuating the myocyte renin-angiotensin system and stretch-mediated apoptosis.

Insulin-like growth factor (IGF)-1 inhibits apoptosis, but its mechanism is unknown. Myocyte stretching activates p53 and p53-dependent genes, leading to the formation of angiotensin II (Ang II) and apoptosis. Therefore, this in vitro system was used to determine whether IGF-1 interfered with p53 function and the local renin-angiotensin system (RAS), decreasing stretch-induced cell death. A single dose of 200 ng/ml IGF-1 at the time of stretching decreased myocyte apoptosis 43% and 61% at 6 and 20 hours. Ang II concentration was reduced 52% at 20 hours. Additionally, p53 DNA binding to angiotensinogen (Aogen), AT1 receptor, and Bax was markedly down-regulated by IGF-1 via the induction of Mdm2 and the formation of Mdm2-p53 complexes. Concurrently, the quantity of p53, Aogen, renin, AT1 receptor, and Bax was reduced in stretched myocytes exposed to IGF-1. Conversely, Bcl-2 and the Bcl-2-to-Bax protein ratio increased. The effects of IGF-1 on cell death, Ang II synthesis, and Bax protein were the consequence of Mdm2-induced down-regulation of p53 function. In conclusion, the anti-apoptotic impact of IGF-1 on stretched myocytes was mediated by its capacity to depress p53 transcriptional activity, which limited Ang II formation and attenuated the susceptibility of myocytes to trigger their endogenous cell death pathway.

Angiotensin II↗
PubMed1999

Models and remodeling: mechanisms and clinical implications.

Ventricular remodeling is a process by which the size, shape and composition of cardiac chambers as well as the thickness and composition of the walls are altered in response to physical loads and/or receptor activation, whether created by loss or overload of cardiac myocytes, or the effects of external hormonal or chemical factors. Involved in this process are hypertrophy, dilation, myocyte loss whether due to necrosis or apoptosis, and myocyte hyperplasia. The present review discusses the dynamic and plastic structure of the heart in its capacity to respond to loading. The mechanisms by which myocyte growth as well as myocyte loss are mediated offer therapeutic opportunities to alter these events.

Animals↗
PubMed1999

Activation of cyclins and cyclin-dependent kinases, DNA synthesis, and myocyte mitotic division in pacing-induced heart failure in dogs.

The inability of myocytes to reenter the cell cycle in vitro may result from a block in the activation of cyclins and cyclin-dependent kinases (cdk). This inhibition may not occur in vivo because myocyte proliferation is present in the failing heart. Thus, cardiac failure was induced by ventricular pacing in dogs, and changes in the quantity of cyclin D2, cyclin A, cyclin B, cdk2, and cell-division cycle-2 (cdc2) in control and paced myocytes were measured. The kinase activity of these nuclear proteins was also established. Finally, DNA synthesis and mitotic indices in myocytes were evaluated. Cyclin D2 in myocytes increased 7-fold after pacing, and cyclin D2-associated kinase activity increased 3-fold. Similarly, cyclin A quantity and activity increased 4-fold. Comparable changes were observed for cyclin B. cdc2 protein increased 8-fold, and cdk2 and cdc2 activity increased 3-fold and 5-fold, respectively. DNA synthesis was detected in 556 myocyte nuclei/10(6) and 2,467 myocyte nuclei/10(6) in control and paced hearts, respectively. Corresponding mitotic indices were 16/10(6) and 95/106, respectively. In conclusion, myocytes react to cardiac failure by activating cyclins and cdk, which are coupled with cell regeneration and the recovery of muscle mass.

Animals↗
PubMed1998

Coronary artery constriction in rats: necrotic and apoptotic myocyte death.

The purpose of this study was to determine whether coronary artery narrowing was associated with the activation of necrotic and apoptotic myocyte cell death in the myocardium and whether these 2 forms of cell death were restricted to the left ventricle, or involved the other portions of the heart. Coronary artery narrowing was surgically induced in rats, and the animals were killed from 45 minutes to 12 days after surgery. Myocyte apoptosis was detected by the terminal deoxynucleotidyl transferase assay, confocal microscopy, and deoxyribonucleic acid (DNA) agarose gel electrophoresis. Myocyte necrosis was identified by myosin monoclonal antibody labeling of the cytoplasm. A separate group of animals was treated with trimetazidine in an attempt to interfere with tissue injury. Coronary artery narrowing was characterized by myocyte apoptosis in the left ventricle and interventricular septum, which progressively increased from 45 minutes to 6 days. However, apoptosis was not observed at 12 days. Conversely, myocyte necrosis reached its maximum value at 1 day and was still present at 12 days. This form of cell death affected not only the left ventricular free wall and interventricular septum, but also the right ventricle. Cell necrosis markedly exceeded apoptosis at all intervals. At the peak of cell death, myocyte necrosis was 52-fold and 33-fold higher than apoptosis in the left ventricle and septum. In conclusion, necrotic myocyte cell death is the prevailing form of damage produced by coronary artery narrowing, but apoptotic cell death contributes to the loss of myocytes in the ischemic heart. Trimetazidine treatment attenuated the extent of myocardial damage produced by global ischemia.

Animals↗
PubMed1998

Myocyte proliferation in end-stage cardiac failure in humans.

Introduced several decades ago, the dogma persists that cardiac myocytes are terminally differentiated cells and that division of muscle cells is impossible in the adult heart. More recently, nuclear mitotic divisions in myocytes occasionally were seen, but those observations were challenged on the assumption that the rate of cell proliferation was inconsequential for actual tissue regeneration. Moreover, mitoses were never detected in normal myocardium. However, the analysis of routine histologic preparations constituted the basis for the belief that myocytes were unable to reenter the cell cycle and divide, ignoring the limitations of these techniques. We report here by confocal microscopy that 14 myocytes per million were in mitosis in control human hearts. A nearly 10-fold increase in this parameter was measured in end-stage ischemic heart disease (152 myocytes per million) and in idiopathic dilated cardiomyopathy (131 myocytes per million). Because the left ventricle contains 5.8 x 10(9) myocytes, these mitotic indices imply that 81.2 x 10(3), 882 x 10(3), and 760 x 10(3) myocytes were in mitosis in the entire ventricular myocardium of control hearts and hearts affected by ischemic and idiopathic dilated cardiomyopathy, respectively. Additionally, mitosis lasts less than 1 hr, suggesting that large numbers of myocytes can be formed in the nonpathologic and pathologic heart with time. Evidence of cytokinesis in myocytes was obtained, providing unequivocal proof of myocyte proliferation.

Adult↗
PubMed1998

Angiotensin II stimulation in vitro induces hypertrophy of normal and postinfarcted ventricular myocytes.

To determine whether angiotensin II (Ang II) stimulation of adult ventricular myocytes in vitro results in cellular hypertrophy, the changes in myocyte volume and protein content per cell were examined by confocal microscopy. Moreover, the possibility was considered that the upregulation of Ang II receptors on myocytes after infarction may potentiate and/or accelerate Ang II-mediated myocyte growth. Left ventricular myocytes isolated from control and failing hearts 3 days after infarction were cultured for 3 and 7 days in the presence of Ang II. Normal myocytes did not show an increase in volume and protein content at 3 days, but a 16% and 20% increase in these respective parameters was found at 7 days. Cell growth was faster and greater in myocytes from postinfarcted hearts. In these cells, myocyte volume increased 23% and protein content increased 28% at 3 days after Ang II administration. The higher hypertrophic reaction of myocytes from infarcted hearts occurred in spite of a 19% larger volume at isolation. In both groups of myocytes, the AT1 receptor blocker losartan completely inhibited the consequences of Ang II. Conversely, the AT2 receptor antagonist PD123319 had no effect on Ang II-induced hypertrophy. In conclusion, Ang II promotes myocyte growth through the activation of AT1 receptors, which modulate the time and magnitude of this cellular response.

Angiotensin II↗