- Novel mechanisms of G-protein-coupled receptors functions: AT1 angiotensin receptor acts as a signaling hub and focal point of receptor cross-talk. [Review]
- BPBest Pract Res Clin Endocrinol Metab 2018; 32(2):69-82
- AT1 angiotensin receptor (AT1R), a prototypical G protein-coupled receptor (GPCR), is the main receptor, which mediates the effects of the renin-angiotensin system (RAS). AT1R plays a crucial role in...
AT1 angiotensin receptor (AT1R), a prototypical G protein-coupled receptor (GPCR), is the main receptor, which mediates the effects of the renin-angiotensin system (RAS). AT1R plays a crucial role in the regulation of blood pressure and salt-water homeostasis, and in the development of pathological conditions, such as hypertension, heart failure, cardiovascular remodeling, renal fibrosis, inflammation, and metabolic disorders. Stimulation of AT1R leads to pleiotropic signal transduction pathways generating arrays of complex cellular responses. Growing amount of evidence shows that AT1R is a versatile GPCR, which has multiple unique faces with distinct conformations and signaling properties providing new opportunities for functionally selective pharmacological targeting of the receptor. Biased ligands of AT1R have been developed to selectively activate the β-arrestin pathway, which may have therapeutic benefits compared to the conventional angiotensin converting enzyme inhibitors and angiotensin receptor blockers. In this review, we provide a summary about the most recent findings and novel aspects of the AT1R function, signaling, regulation, dimerization or oligomerization and its cross-talk with other receptors, including epidermal growth factor (EGF) receptor, adrenergic receptors and CB1 cannabinoid receptor. Better understanding of the mechanisms and structural aspects of AT1R activation and cross-talk can lead to the development of novel type of drugs for the treatment of cardiovascular and other diseases.
- [Bradykinin and cardiovascular protection. Role of perindopril, an inhibitor of angiotensin conversion enzyme]. [Classical Article]
- RMRev Med Liege 2018; 73(4):197-205
- The endothelium plays a vital role as part of the cardiovascular continuum. Risk factors such as hypertension and dyslipidemia unbalance angiotensin II - bradykinin homeostasis, leading to endothelia...
The endothelium plays a vital role as part of the cardiovascular continuum. Risk factors such as hypertension and dyslipidemia unbalance angiotensin II - bradykinin homeostasis, leading to endothelial dysfunction and changes in vascular structure that promote atherosclerosis and thrombosis. When dealing with risk factors, treatment should focus on the prevention and restoration of endothelial function. Not all cardiovascular drugs are able to reverse vascular and structural endothelial dysfunction. Increasing levels of bradykinin is an effect of the use of angiotensin-converting enzyme inhibitors (ACE-Is), and also a fundamental part of their mode of action. The cardiovascular protection observed with ACE-I, and not with sartans, can be explained rationally by the specific effects of bradykinin on the endothelium. In the pharmacological class of ACE-Is, perindopril likely produces the strongest effects on bradykinin, which may explain, at least in part, the documented superiority of this drug in the prevention and treatment of cardiovascular disease.
- [Acquired C1 esterase inhibitor deficiency via bradykinin-mediated angioedema: Four cases]. [Journal Article]
- ADAnn Dermatol Venereol 2018 Apr 16
- CONCLUSIONS: C1-INH-AAE induced by ACE inhibitors or ARBs may be associated with hematologic malignancies. This form of revelation does not necessarily indicate a diagnosis of ACE or ARBs angioedema, and screening should therefore be performed for C1 Inh and C1q. An underlying hematologic malignancy should be routinely sought and the long-term prognosis determined.
- [Can we prevent heart failure in women with antihypertensive treatment?]. [Journal Article]
- PLPrzegl Lek 2016; 73(6):419-23
- Arterial hypertension has beenlong considered as one of the most common etiological conditions predisposing to the development of heart failure. Until the middle of the last century, almost a half of...
Arterial hypertension has beenlong considered as one of the most common etiological conditions predisposing to the development of heart failure. Until the middle of the last century, almost a half of the all deaths caused by arterial hypertension were related with heart failure. Natural history of hypertension leads to heart failure in two main mechanisms. One of them is hypertension induced left ventricular hypertrophy and fibrosis, progressive deterioration of left ventricular compliance, increase in left ventricular enddiastolic pressure which in turn lead to left ventricular diastolic dysfunction. The other pathomechanism of heart failure associated to hypertension is accelerated coronary artery atherosclerosis, ischemia of the left ventricle and its systolic dysfunction. In women, prevalence of heart failure related to diastolic dysfunction (with preserved ejection fraction) is more common than heart failure with reduced ejection fraction. There are no specific guidelines for treating clinically overt diastolic heart failure, but pharmacological treatment should be directed at normalizing blood pressure, promoting regression of hypertrophy, preventing tachycardia and treating symptoms of congestion. Preventive strategies directed toward an early and aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of diastolic heart failure. The other type of potentially preventable heart failure may be related with cardiotoxicity of anticancer medication. Hypertension is a known factor strongly increasing the risk of cardiotoxicity of chemotherapy. Each women with arterial hypertension undergoing radio- or chemotherapy of cancer should achieve optimal blood pressure control before and during the oncological treatment. There are strong evidence that treatment with angiotensin converting enzyme inhibitors protects against chemotherapy induced heart failure.
- Incidence, predictors and clinical management of hyperkalaemia in new users of mineralocorticoid receptor antagonists. [Journal Article]
- EJEur J Heart Fail 2018 Apr 18
- CONCLUSIONS: Among real-world adults initiating MRA therapy, hyperkalaemia was very common and frequently followed by therapy interruption, especially among participants with CKD.
- Efficacy and Safety of Zofenopril Versus Ramipril in the Treatment of Myocardial Infarction and Heart Failure: A Review of the Published and Unpublished Data of the Randomized Double-Blind SMILE-4 Study. [Review]
- ATAdv Ther 2018 Apr 17
- Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on e...
Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical efficacy and safety have been described in the four randomized controlled trials of the SMILE program, which globally enrolled more than 3600 patients in post-acute myocardial infarction (AMI) setting. The SMILE-4 study specifically selected patients with left ventricular dysfunction at admission, and compared the effects of zofenopril or ramipril in combination with acetylsalicylic acid (ASA). Zofenopril demonstrated its superiority over ramipril in reducing the combined occurrence of death or hospitalization for cardiovascular causes both in the overall population included in the original study and in subgroups of patients at highest risk, namely hypertensive and diabetic subjects. The effects of the early treatment with zofenopril were sustained over time, and, after 5 years of follow-up, zofenopril increased the survival likelihood and reduced the hospitalization rate. Compared to ramipril, zofenopril was cost-effective with a number to treat of 13 and an incremental cost-effectiveness ratio (ICER) of 2125.45 euros for any additional event prevented. Furthermore, in real-world settings, zofenopril decreased the risk of death in patients with heart failure, particularly in men, and in subjects older than 76 years or with ejection fraction lower than 54%. These results support the early use of zofenopril immediately after AMI, even in the presence of comorbidities, and its maintenance over time to reduce the risk of heart failure.
- Intervention using vitamin D for elevated urinary albumin in type 2 diabetes mellitus (IDEAL-2 Study): study protocol for a randomised controlled trial. [Journal Article]
- TTrials 2018 Apr 17; 19(1):230
- CONCLUSIONS: If the addition of calcitriol to RAAS inhibition with ACEI or ARB safely results in a significant reduction in albuminuria, the study adds to the body of evidence supporting a role for vitamin D in reno-protection, will inform clinical practice and could result in significant reduction of healthcare costs associated with DKD.
- Acute kidney injury during treatment with high-dose cloxacillin: A report of 23 cases and literature review. [Journal Article]
- IJInt J Antimicrob Agents 2018 Apr 14
- CONCLUSIONS: AKI during high-dose cloxacillin treatment mostly occurs in elderly patients, with concomitant nephrotoxic drugs. The outcome is usually favorable after cloxacillin discontinuation. Therapeutic drug monitoring may decrease the risk of AKI in patients treated with high-dose cloxacillin.
- Peripheral arterial disease: Changes in clinical outcomes and therapeutic strategies in two cohorts, from 2002 to 2008 and from 2008 to 2014. A population-based study. [Journal Article]
- EJEur J Prev Cardiol 2018 Jan 01; :2047487318770299
- Background The aim of our study was to evaluate whether treatments for peripheral artery disease changed in two different cohorts identified in 2002 and 2008, and whether this had an impact on mortal...
Background The aim of our study was to evaluate whether treatments for peripheral artery disease changed in two different cohorts identified in 2002 and 2008, and whether this had an impact on mortality and major clinical outcomes after six years of follow-up. Methods Using administrative health databases of the largest region in Northern Italy, we identified patients admitted to hospital for peripheral artery disease in 2002 and 2008. Both cohorts were followed for six years. All cause death, acute coronary syndrome, stroke and major amputations, cardiovascular prevention drugs and revascularization procedures were collected. Incidence of events was plotted using adjusted cumulative incidence function estimates. The risk, for each outcome, was compared between 2002-2008 and 2008-2014 using a multivariable Fine and Gray's semiparametric proportional subdistribution hazards model. Results In 2002 and 2008, 2885 and 2848 patients were identified. Adjusting for age, sex, Charlson comorbidity index and severity of peripheral artery disease we observed a significant reduction (in 2008 vs. 2002) in the risk of acute coronary syndrome (28%), stroke (27%) and major amputation (17%). No change was observed in the risk of death. The percentages of patients with peripheral artery revascularizations, during the hospital stay, increased: 43.8% in 2002 vs. 49.0% in 2008, p < 0.001. From 2002 to 2008 there was a significant absolute increase in the prescription of lipid-lowering drugs (+18%), antiplatelets (+7.2%) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (+11.8%), p < 0.001. Conclusions In six years of follow-up we observed a reduction in risk of major cardiovascular events in 2008-2014 in comparison with the 2002-2008 cohort. Increasing use of revascularization interventions and cardiovascular prevention drugs could have contributed to the better prognosis.
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- Do practice gaps exist in evidence-based medication prescription at hospital discharge in patients undergoing coronary artery bypass surgery & coronary angioplasty? [Journal Article]
- IJIndian J Med Res 2017; 146(6):722-729
- CONCLUSIONS: Significant differences in prescription of GDMT between PCI and CABG patients existed at hospital discharge. A substantial proportion of post-CABG patients did not receive BB and/or statins. These patients were also less likely to receive high-dose statin or optimal BB dose and more likely to routinely receive clopidogrel and diuretics. Such deviations from GDMT need to be rectified to improve quality of cardiac care after coronary revascularization.