Aging and Remodeling of the RAS and RAAS and Related Pathways: Implications for Heart Failure Therapy

Jugdutt, Bodh I.

doi:10.1007/978-1-4939-0268-2_18

Cited by 7 publications

(7 citation statements)

References 241 publications

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“…This possibility opens up a new area of research into other biologically active peptides. The authors have suggested testing for interactions of VIF with other angiotensin peptides (such as angiotensinogen, Ang-II, Ang-III, Ang-IV, and Ang- [1][2][3][4][5][6][7]), angioprotectin, and alamandine.…”

Section: Expanding Saga Of the Renin-angiotensin Systemmentioning

confidence: 99%

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Expanding Saga of the Renin-Angiotensin System

Jugdutt

2015

Circulation

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Section: Expanding Saga Of the Renin-angiotensin Systemmentioning

confidence: 99%

“…5 Importantly, aging is associated with RAS dysregulation and increased Ang-II and other RAS components, which in turn may contribute to increased cardiovascular remodeling and risk in elderly patients. 4,5 In diabetic nephropathy, excessive RAAS activation results in progressive renal damage.…”

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confidence: 99%

Expanding Saga of the Renin-Angiotensin System

Jugdutt

2015

Circulation

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“…LCZ696 was shown to benefit patients with HFpEF in a phase II trial [103,104] and is being evaluated in patients with HFrEF in a phase III trial [103,104]. Since is associated with RAAS remodeling [105], whether dual pathway inhibition and other RAAS and novel therapies may be more effective in elderly HF patients needs study.…”

Section: Therapy and Modulators Of Post-mi Remodeling And Markers Witmentioning

confidence: 99%

Aging-related Changes in Cardiac Extracellular Matrix: Implications for Heart Failure in Older Patients

Jugdutt¹

2015

JCCR

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The aging population with heart failure (HF) is increasing worldwide. Hypertension (HTN) and myocardial infarction (MI) are the two main comorbidities leading to HF in the elderly (age ≥ 65 years). Aging is progressive and results in cardiovascular changes that lead to an aging phenotype and negatively impact disease expression and response to therapy. Aging-related changes contribute to adverse cardiac remodeling and HF with preserved ejection fraction (HFpEF). HTN also leads to HFpEF whereas MI leads to HF with reduced EF (HFrEF). Aging and concomitant HTN or MI accelerates the march to HF. The cardiac extracellular matrix (ECM) is critical for maintaining cardiac shape/function. A key mechanism in the development and progression of HF due MI and HTN involves adverse cardiac ECM remodeling. Disruption of the ECM network and dysregulation of ECM homeostasis and metabolism result in adverse cardiac remodeling with shape deformation and dysfunction that lead to HF, disability and death. Agingrelated cardiac remodeling with superimposed progressive left ventricular remodeling leading to HFpEF or HFrEF in older patients is a persistent problem that has important therapeutic implications. Studies suggest that in the elderly, novel pathways can be targeted for optimizing therapy in HFrEF post-MI and HFpEF post-HTN. Therapeutic strategies that include targeting of adverse cardiac ECM remodeling could prevent/limit/reverse progression to HF in aging patients.

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“…Increased AngII after MI and the arrhythmogenic effect of AngII acting via AT 1 R are well documented [6,[22][23][24]. The postulated mechanisms have centered around limitations of infarct size, adverse post-MI infarct zone and structural LV remodeling [6,18,24] and electrical remodeling [1][2][3][4][5][6][7]. Recent experimental studies with valsartan post MI documented decreased AT 1 R expression, decreased fibrosis and restored connexin43 in the border zone and reduced PES-induced VAs [25], and reduced transmural dispersion of repolarization and electrical heterogeneity with preserved the density of the outward potassium current (Ito) [26].…”

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confidence: 99%

“…Confirmation in large animal models is also needed. Since the animals were young, confirmation in older animals is needed because significant remodeling of the RAAS and other pathways occur with aging [24] and may involve post-MI electrical remodeling as well. There is extensive evidence that significant structural remodeling occurs during the acute as well as the subacute healing/repair phase after MI depending on infarct size as well as adequacy of healing/repair.…”

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Suppression of Ventricular Arrhythmias After Myocardial Infarction by AT1 Receptor Blockade: Role of the AT2 Receptor and Casein Kinase 2/Kir2.1 Pathway

Jugdutt

2015

Cardiovasc Drugs Ther

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Abbreviations AADHowever, the precise molecular mechanism for the ARBinduced suppression of VAs has been elusive. A major goal of translational research has therefore been to not only unravel the underlying molecular mechanisms for post-MI VAs in general, but also to identify the precise molecular mechanisms and novel pathways resulting in their suppression so that they may be specifically targeted. There is a definite need for new therapies because a significant percentage of post-MI survivors continue to develop VAs resulting in SCD or Bfinald eath despite optimal therapy including reperfusion [4,7]. The electrical mechanisms of post-MI VAs have been extensively studied in experimental models since the 1980s. The traditional concept for VA induction in both MI and non-MI hearts has revolved around reentry, triggers and substrates [8][9][10][11][12]. Most cardiology students are familiar with the simple form of re-entry due to an anatomic obstacle described by Mines in 1913, and the classic Schmitt-Erlanger model of unidirectional block and re-entry proposed in 1929. However, MI is rather unique in that it results in variable degrees of regional remodeling of myocardial structure, matrix, morphology, topography and electrophysiological

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Aging and Remodeling of the RAS and RAAS and Related Pathways: Implications for Heart Failure Therapy

Cited by 7 publications

References 241 publications

Expanding Saga of the Renin-Angiotensin System

Expanding Saga of the Renin-Angiotensin System

Aging-related Changes in Cardiac Extracellular Matrix: Implications for Heart Failure in Older Patients

Suppression of Ventricular Arrhythmias After Myocardial Infarction by AT1 Receptor Blockade: Role of the AT2 Receptor and Casein Kinase 2/Kir2.1 Pathway

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