Genetic Variation Within Adrenergic Pathways Determines In Vivo Effects of Presynaptic Stimulation in Humans

Fung, Maple M.; Nguyen, Carie; Mehtani, Parag; Salem, Rany M.; Perez, Brandon; Thomas, Brenda; Das, Madhusudan; Schork, Nicholas J.; Mahata, Sushil K.; Ziegler, Michael G.; O’Connor, Daniel T.

doi:10.1161/circulationaha.107.706317

Cited by 17 publications

(13 citation statements)

References 52 publications

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“…Cardiac response may be significantly coupled to genetic differences at candidate loci that encode components of the catecholamine biosynthesis, storage, and metabolic pathway. The large interindividual differences may reflect variable responses to sympathetic activity, it may be accounted for by genetic inheritance, and it may play a role in the development of SICM [31]. This is a still relatively unknown field worth investigation to understand SICM, malignant arrhythmias and related cardiac arrest [32,33].…”

Section: Resultsmentioning

confidence: 99%

Insight into stress-induced cardiomyopathy and sudden cardiac death due to stress. A forensic cardio-pathologist point of view

Fineschi

Michalodimitrakis

D’Errico

et al. 2010

Forensic Science International

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Section: Resultsmentioning

confidence: 99%

Insight into stress-induced cardiomyopathy and sudden cardiac death due to stress. A forensic cardio-pathologist point of view

Fineschi

Michalodimitrakis

D’Errico

et al. 2010

Forensic Science International

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“…In contrast, a polymorphism in the CgB gene was reported to be the strongest predictor of enhanced vasoconstriction in a study assessing association between single nucleotide polymorphisms in the adrenergic pathway and venous vasoconstriction. 35 The net effect of increased circulating CgB levels in HF patients with regard to autonomic nervous system tone is not clear and will require additional investigations. Increased CgB levels may also have direct effects on the cardiomyocytes and the myocardium.…”

Section: Discussionmentioning

confidence: 99%

Chromogranin B in Heart Failure

Røsjø

Husberg

Dahl

et al. 2010

Circ: Heart Failure

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Background-Chromogranin B (CgB) is a member of the granin protein family. Because CgB is often colocalized with chromogranin A (CgA), a recently discovered cardiac biomarker, we hypothesized that CgB is regulated during heart failure (HF) development. Methods and Results-CgB regulation was investigated in patients with chronic HF and in a post-myocardial infarction HF mouse model. Animals were phenotypically characterized by echocardiography and euthanized 1 week after myocardial infarction. CgB mRNA levels were 5. Key Words: heart failure Ⅲ molecular biology Ⅲ biological markers Ⅲ chromogranin B A dvances in treatment of acute coronary syndromes have reduced short-term mortality following acute myocardial infarction (MI), but at the cost of a higher incidence of post-MI heart failure (HF). 1 Improved pathophysiological understanding of HF and better tools for risk prediction and diagnostic purposes are therefore needed. 2 The cardiac biomarkers used routinely in clinical practice today are proteins specific to the diseased myocardium, either released during cell necrosis (cardiac specific troponins) 3 or secreted secondary to cardiomyocyte strain (B-type natriuretic peptide, BNP). 4 However, there is still a need for markers reflecting other pathophysiological processes in heart disease. 5 Thus, identifying new proteins regulated in the failing myocardium may potentially improve both the understanding of HF development and lead to the discovery of novel cardiac biomarkers. Clinical Perspective on p 511Chromogranin B (CgB) is a 50-kDa protein belonging to a group of acidic proteins called the granin protein family. 6 The most extensively studied and well-known member of the granin family is chromogranin A (CgA), a protein currently used clinically as a biomarker in patients with neuroendocrine tumors. 7 Recently, CgA has been shown to increase with the severity of HF 8 and to be an independent predictor of mortality in patients with acute coronary syndrome. 9 -11 Moreover, increased CgA production has been demonstrated in cardiomyocytes of the failing myocardium. 12 However, a confounding factor possibly reducing CgA's merit as a cardiac biomarker is the increase in CgA levels seen with the use of proton pump inhibitors (PPIs). 13 In contrast, CgB Methods Mouse Model of HFA permanent ligation of the left main coronary artery were performed in mice in the HF group, whereas sham-operated (sham) animals underwent the same procedure except ligation of the coronary artery. 16 Echocardiographic examination was performed 1 week after the primary operation. The criteria for including animals in the HF group have previously been validated. 17

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“…5 The importance of the control of norepinephrine release was demonstrated recently in humans, where family history of hypertension and genetic variations in proteins involved in presynaptic catecholamine synthesis, storage, and metabolism predicted the constrictory response to tyramine in dorsal hand veins. 19 Furthermore, ICI-118551 (␤ 2 ) reduced BP in moderately hypertensive patients. 20…”

Section: Catecholamine Releasementioning

confidence: 98%

Role of β _1–3 -Adrenoceptors in Blood Pressure Control at Rest and During Tyramine-Induced Norepinephrine Release in Spontaneously Hypertensive Rats

2010

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beta-Adrenoceptors contribute to hypertension in spite of the fact that beta-adrenoceptor agonists lower blood pressure. We aimed to differentiate between these functions and to identify differences between spontaneously hypertensive and normotensive rats. beta-Adrenoceptor antagonists with different subtype selectivity or the ability to cross the blood-brain barrier were used to demonstrate beta-adrenoceptor involvement in resting blood pressure and the response to tyramine-induced peripheral norepinephrine release. The centrally acting propranolol (beta(1+2[+3])), CGP20712A (beta(1)), ICI-118551 (beta(2)), and SR59230A (beta(3)), as well as peripherally restricted nadolol (beta(1+2)) and atenolol (beta(1)), were administered intravenously, separately, or in combinations. Blood pressure, cardiac output, heart rate, total peripheral vascular resistance, and plasma catecholamine concentrations were evaluated. beta-Adrenoceptor antagonists had little effect on cardiovascular baselines in normotensive rats. In hypertensive rats, antagonist-induced hypotension paralleled reductions in resistance, except for atenolol, which reduced cardiac output. The resistance reduction involved primarily neuronal catecholamine, central beta(1)-adrenoceptors, and peripheral beta(2)-adrenoceptors. Tyramine induced a transient, prazosin-sensitive vascular resistance increase. Inhibition of nerve-activated, peripheral beta(1/3)-adrenoceptors enhanced this alpha(1)-adrenoceptor-dependent vasoconstriction in normotensive but not hypertensive rats. In hypertensive rats, return to baseline was eliminated after inhibition of the central beta(1)-adrenoceptor, epinephrine release (acute adrenalectomy), and peripheral beta(2/3)-adrenoceptors. Adrenalectomy eliminated beta-adrenoceptor-mediated vasodilation in hypertensive rats, and tyramine induced a prazosin-sensitive vasoconstriction, which was inhibited by combined blockade of central beta(1)- and peripheral beta(2)-adrenoceptors. In conclusion, nerve-activated beta(1)- and beta(3)-adrenoceptor-mediated vasodilation was not present in hypertensive rats, whereas epinephrine-activated beta(2)- and beta(3)-adrenoceptor-mediated vasodilation was upregulated. There was also a hypertensive, nerve-activated vasoconstrictory mechanism present in hypertensive rats, involving central beta(1)- and peripheral beta(2)-adrenoceptors combined.

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Genetic Variation Within Adrenergic Pathways Determines In Vivo Effects of Presynaptic Stimulation in Humans

Abstract: Background-Catecholamines

Cited by 17 publications

References 52 publications

Insight into stress-induced cardiomyopathy and sudden cardiac death due to stress. A forensic cardio-pathologist point of view

Insight into stress-induced cardiomyopathy and sudden cardiac death due to stress. A forensic cardio-pathologist point of view

Chromogranin B in Heart Failure

Role of β _1–3 -Adrenoceptors in Blood Pressure Control at Rest and During Tyramine-Induced Norepinephrine Release in Spontaneously Hypertensive Rats

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Genetic Variation Within Adrenergic Pathways Determines In Vivo Effects of Presynaptic Stimulation in Humans

Abstract: Background-Catecholamines

Cited by 17 publications

References 52 publications

Insight into stress-induced cardiomyopathy and sudden cardiac death due to stress. A forensic cardio-pathologist point of view

Insight into stress-induced cardiomyopathy and sudden cardiac death due to stress. A forensic cardio-pathologist point of view

Chromogranin B in Heart Failure

Role of β 1–3 -Adrenoceptors in Blood Pressure Control at Rest and During Tyramine-Induced Norepinephrine Release in Spontaneously Hypertensive Rats

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Product

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Role of β _1–3 -Adrenoceptors in Blood Pressure Control at Rest and During Tyramine-Induced Norepinephrine Release in Spontaneously Hypertensive Rats