The Treatment of Cardiovascular Disease Continuum: Focus on Pharmacologic Management and RAS Blockade

Chrysant, Steven G.; Chrysant, George S.; Chrysant, Catherine; Shiraz, Mohammad Feili

doi:10.2174/157488410791110742

Cited by 30 publications

(23 citation statements)

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“…ARBs protect end organs not only because they ameliorate hypertension, but also as a consequence of beneficial effects on associated inflammatory and metabolic alterations beyond their effect on blood pressure control [2,3]. The protective effect of ARBs is enhanced with increasing doses beyond full AT 1 blockade [4], suggesting beneficial mechanisms additional to AT 1 blockade.…”

Section: Introductionmentioning

confidence: 99%

Telmisartan ameliorates lipopolysaccharide-induced innate immune response through peroxisome proliferator-activated receptor-γ activation in human monocytes

Pang

Benický

Wang

et al. 2012

Journal of Hypertension

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Objective Angiotensin II type 1 receptor (AT1) blockers (ARBs) reduce the bacterial endotoxin lipopolysaccharide (LPS)-induced innate immune response in human circulating monocytes expressing few AT1. To clarify the mechanisms of anti-inflammatory effects of ARBs with different peroxisome proliferator-activated receptor-γ (PPARγ)-activating potencies, we focused our study on telmisartan, an ARB with the highest PPARγ-stimulating activity. Methods Human circulating monocytes and monocytic THP-1 (human acute monocytic leukemia cell line) cells were exposed to 50 ng/ml LPS with or without pre-incubation with telmisartan. AT1 mRNA and protein expressions were determined by real-time PCR and membrane receptor binding assay, respectively. The expression of pro-inflammatory factors was determined by real-time PCR, western blot analysis and ELISA. PPARγ activation was measured by electrophoretic mobility shift assay and its role was determined by pharmacological inhibition and PPARγ gene silencing. Results In human monocytes, telmisartan significantly attenuated the LPS-induced expression of pro-inflammatory factors, the release of pro-inflammatory cytokines and prostaglandin E2, nuclear factor-κB activation and reactive oxygen species formation. In THP-1 cells, telmisartan significantly reduced LPS-induced tumor necrosis factor-α, inhibitor of κB-α, monocyte chemotactic protein-1 (MCP-1) and lectin-like oxidized low-density lipoprotein receptor-1 gene expression and MCP-1-directed migration. Telmisartan also stimulated the expression of the PPARγ target genes cluster of differentiation 36 and ATP-binding cassette subfamily G member 1 in monocytes. The anti-inflammatory effects of telmisartan were prevented by both PPARγ antagonism and PPARγ gene silencing. Anti-inflammatory effects of ARBs correlated with their PPARγ agonist potency. Conclusion Our observations demonstrate that in human monocytes, ARBs inhibit the LPS-induced pro-inflammatory response to a major extent through the PPARγ activation pathway and may be beneficial for the treatment of cardiovascular and metabolic disorders in which inflammation plays a major role.

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Section: Introductionmentioning

confidence: 99%

Telmisartan ameliorates lipopolysaccharide-induced innate immune response through peroxisome proliferator-activated receptor-γ activation in human monocytes

Pang

Benický

Wang

et al. 2012

Journal of Hypertension

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“…New antidiabetic agents such as GLP-1 agonists and sodium glucose transporter-2 (SGLT-2) inhibitors result in some weight loss and are candidate drugs particularly in metabolic syndrome patients with or at risk for diabetes [39,40]. RAS blockers are effective in decreasing blood pressure and other cardiovascular risk [41]. Cilostazol, an antiplatelet agent, is also known to improve atherogenic dyslipidemia and increase nitric oxide levels [42].…”

Section: Pharmacological Treatment Of Metabolic Syndromementioning

confidence: 99%

Pharmacological treatment and therapeutic perspectives of metabolic syndrome

Lim

Eckel

2014

Rev Endocr Metab Disord

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Metabolic syndrome is a disorder based on insulin resistance. Metabolic syndrome is diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal obesity, elevated blood pressures, elevated glucose, high triglycerides, and low high-density lipoprotein-cholesterol (HDL-C) levels. Clinical implication of metabolic syndrome is that it increases the risk of developing type 2 diabetes and cardiovascular diseases. Prevalence of the metabolic syndrome has increased globally, particularly in the last decade, to the point of being regarded as an epidemic. The prevalence of metabolic syndrome in the USA is estimated to be 34% of adult population. Moreover, increasing rate of metabolic syndrome in developing countries is dramatic. One can speculate that metabolic syndrome is going to induce huge impact on our lives. The metabolic syndrome cannot be treated with a single agent, since it is a multifaceted health problem. A healthy lifestyle including weight reduction is likely most effective in controlling metabolic syndrome. However, it is difficult to initiate and maintain healthy lifestyles, and in particular, with the recidivism of obesity in most patients who lose weight. Next, pharmacological agents that deal with obesity, diabetes, hypertension, and dyslipidemia can be used singly or in combination: anti-obesity drugs, thiazolidinediones, metformin, statins, fibrates, renin-angiotensin system blockers, glucagon like peptide-1 agonists, sodium glucose transporter-2 inhibitors, and some antiplatelet agents such as cilostazol. These drugs have not only their own pharmacologic targets on individual components of metabolic syndrome but some other properties may prove beneficial, i.e. anti-inflammatory and anti-oxidative. This review will describe pathophysiologic features of metabolic syndrome and pharmacologic agents for the treatment of metabolic syndrome, which are currently available.

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“…Therefore, a more complete inhibition of RAAS was expected to provide significantly more cardiovascular gains, since Ang II is considered a major contributor to cardiovascular disease continuum [34]. Therefore, the dual RAAS blockers have been used extensively, besides hypertension, also for the treatment of a variety of cardiovascular diseases including CHD with LVD or HF with mixed results.…”

Section: Cardiovascular Effects Of Dual Raas Blockade In Patients Witmentioning

confidence: 99%

Dual Renin-Angiotensin-Aldosterone Blockade: Promises and Pitfalls

Chrysant

2014

Curr Hypertens Rep

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Single renin-angiotensin-aldosterone system (RAAS) blockade has been shown to be effective and safe for the treatment of hypertension, coronary heart disease (CHD), heart failure (HF), diabetes, and chronic kidney disease (CKD) with proteinuria. Due to the action of RAAS blockers at various levels of the RAAS cascade, it was hypothesized that dual RAAS blockade would result in more complete inhibition of angiotensin II (Ang II) production and be more effective in blocking its detrimental cardiovascular remodeling effects. Unfortunately, several clinical trials in patients with hypertension, CHD, HF, and CKD with proteinuria have demonstrated no superiority of dual versus single RAAS blockade, but a higher incidence of adverse events. Based on these findings, dual RAAS blockade is no longer recommended for the routine treatment of various cardiovascular diseases, except diabetic nephropathy with proteinuria and HF with reduced ejection fraction. All the new information gathered from studies within the last 3 years will be presented in this review.

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The Treatment of Cardiovascular Disease Continuum: Focus on Pharmacologic Management and RAS Blockade

Cited by 30 publications

References 0 publications

Telmisartan ameliorates lipopolysaccharide-induced innate immune response through peroxisome proliferator-activated receptor-γ activation in human monocytes

Telmisartan ameliorates lipopolysaccharide-induced innate immune response through peroxisome proliferator-activated receptor-γ activation in human monocytes

Pharmacological treatment and therapeutic perspectives of metabolic syndrome

Dual Renin-Angiotensin-Aldosterone Blockade: Promises and Pitfalls

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