Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Along with menopause goes an increase of cardiovascular heart disease risk, and at the same time a change in certain risk factors. Those risk factor changes are analysed. The most obvious change is cholesterol increase, mostly on its LDL fraction linked to a decrease of its regular epuration. Today, the influence of replacement therapy on cardiovascular heart disease risk is not well known, and this is due mostly to the fact that there are no randomized studies. Thus exists a selection of women with low risk levels, either at the beginning or during follow-up. As a consequence results are necessarily optimized. It is possible to extrapolate the risk factor evolution under treatment only if its mechanism is known. Thus, when estradiol is given not the oral route, lipidic balance is brought back to its premenopausal state, without any noticeable influence on other known risk factors. It is thus reasonable to see there a favorable influence. When estradiol or any other similar molecule is given the oral route, one can notice, depending on the dose and the molecule, similar changes, along however with other variations which actual consequences remain unknown, like the increase of certain coagulation factors, of angiotensinogen, of triglycerides on HDL cholesterol. In particular, one does not know if those last pharmacological changes do not have a negative effect on predisposed patients.
 ...
PMID:[Menopause and cardiovascular risk factors. Influence of treatments]. 161 74

Decreased heart rate variability (HRV) is associated with congestive heart failure, post-myocardial infarction, ventricular arrhythmias, sudden cardiac death, and advancing age. A deletion/insertion polymorphism in the angiotensin-converting enzyme (ACE) gene and a substitution (M235T) in the angiotensinogen gene have been associated with risk for heart disease. The aim of this study was to determine the heritability of HRV and related parameters in monozygotic and dizygotic twins and to assess the influence of ACE and angiotensinogen polymorphisms. We studied 95 MZ pairs and 46 DZ pairs. We measured HRV and related parameters, ACE and angiotensinogen levels, plasma norepinephrine, ACE, and angiotensinogen genotypes. We found that HRV and related parameters were significantly influenced by genetic variability, although nonshared genetic effects were also important. Angiotensinogen and plasma norepinephrine were generally correlated with decreased HRV, whereas ACE was correlated with perturbances of normal rhythmic HRV. Nevertheless, the DD ACE genotype was associated with increased HRV (p <0.05), whereas angiotensinogen polymorphisms had no effect. We conclude that HRV and related parameters are in part heritable. Interestingly, the DD ACE genotype is associated with increased HRV.
 ...
PMID:Angiotensin-converting enzyme and angiotensinogen gene polymorphisms and heart rate variability in twins. 952 87

The importance of the loss of ovarian function to the progression of hypertension and heart disease in women is controversial. We investigated whether ovariectomy would accelerate development of hypertension, congestive heart failure, and neurohumoral activation in adult spontaneous hypertension heart failure (SHHF) rats, a genetic model of heart failure. Six months after ovariectomy, no significant differences between control and ovariectomized rats were seen in systolic or diastolic blood pressure, left ventricular fractional shortening by echocardiography, or heart weight. Percent V1 myosin isozyme was significantly lower in ovariectomized rats. Northern blot analysis failed to show significant differences between groups in expression of hepatic angiotensinogen, renal renin, or left ventricular atrial or brain natriuretic peptide mRNA. In a second experiment, serial measures of systolic pressure and left ventricular shortening fractions failed to document a significant difference between control and ovariectomized rats as they developed heart failure, although there was a significant decline in shortening fraction in both groups at the age when regular estrous cycling naturally ceases. Survival time was similar between groups. In summary, ovariectomy of adult SHHF rats does not appear to affect the progression of genetically programmed hypertension and heart failure in this model.
 ...
PMID:Effect of ovariectomy in heart failure-prone SHHF/Mcc-facp rats. 984 86

Essential hypertension is an escalating problem for industrialized populations. It is currently seen as a 'complex' genetic trait caused by multiple susceptibility genes the effects of which are modulated by gene-environment and gene-gene interactions. Nevertheless, the success to date in identifying these susceptibility genes has been very limited. A number of candidates has been proposed, but demonstrating consistently the linkage or association with hypertension has been problematic. The data for angiotensinogen is undoubtedly the most extensive and meta-analysis has confirmed a significant association overall, although the risk contributed by this gene appears to be modest (odds ratio of 1.2). Identifying further genes - probably conferring even smaller attributable risks - represents a major challenge for future developments in this area. This contrasts markedly with the success that has been achieved in the past 5 years in solving the molecular genetics of a number of rare familial hypertension syndromes. The true incidences of some of these disorders may be higher than first appreciated, but it is still unclear if the genes for these syndromes also play a part in essential hypertension. A more complete understanding of the genetic basis of essential hypertension should be possible in the coming years using new strategies that take advantage of the information provided by the human genome project. This knowledge will irrevocably change the way we approach this disease in terms of its diagnosis, risk assessment for end-points such as stroke and heart disease, and the customised treatment that might be offered in the future.
 ...
PMID:The genetics of essential hypertension. 1116 60

The debate about whether obesity should be called a disease continues. From a clinical perspective, it meets the criteria needed to call it a disease. It has an etiology--an imbalance between energy intake and expenditure. It has a pathogenesis in the feedback systems involving leptin, neurochemicals in the brain, and the neural and endocrine messages that respond to the intake of food. The pathology of obesity lies in its enlarged fat cells, and the pathophysiology lies in the changes in the secretion of products from these enlarged fat cells, including cytokines, procoagulants, inflammatory peptides, and angiotensinogen. These secretory products of fat cells and the increased mass of fat are responsible for the associated metabolic diseases, such as diabetes, hypertension, heart disease, sleep apnea, and some sorts of cancer. Treatments consist of techniques to alter the balance between energy intake and energy expenditure. This constellation of factors leads to the conclusion that obesity should be called a disease.
 ...
PMID:Obesity is a chronic, relapsing neurochemical disease. 1455 29

Hypertension is one of the major health care problems worldwide since it markedly increases the risk for development of heart disease, stroke, generalized vascular disease, and renal failure. The renin-angiotensin system (RAS) with its major end-product angiotensin II (Ang II) plays a fundamental role in blood pressure regulation through direct and indirect mechanisms. Pharmacologically, we can inhibit the RAS using angiotensin-converting enzyme inhibitors and AT1 receptor blocker. Inhibiting renin directly with a clinically useful drug eluded pharmacologists until recently. However, the once-daily, orally effective, small-molecule, direct renin inhibitor aliskiren has recently changed this state of affairs. Aliskiren, with its 40-h half-life and ideal pharmacokinetics, can now address angiotensin production directly at its rate-limiting step. A novel transgenic rat model outfitted with the human renin and angiotensinogen genes allowed the testing of aliskiren in an animal model. Preclinical data demonstrated that aliskiren prolonged survival, decreased cardiac hypertrophy and the inducibility of arrhythmias, proteinuria, and attenuated inflammation. All these features might result in improved target-organ damage. Studies in humans attest to an effective blood pressure-lowering action, a largely side effect-free profile, and the option of several combination therapies. Aliskiren is the first of a novel antihypertensive drug class. The preclinical data is very promising. Nevertheless, for the evaluation of its potency in humans, we have to wait for more clinical data.
 ...
PMID:Aliskiren--mode of action and preclinical data. 1844 51

In addition to its role as an energy storage depot, adipose tissue is now recognized as a complex endocrine organ. Adipose tissue releases a variety of factors, termed adipokines, that regulate energy metabolism, cardiovascular function, reproductive status, and immune function. Some of the better-studied adipokines include leptin, adiponectin, and components of the renin-angiotensin system such as angiotensinogen. The function of more recently discovered adipokines such as resistin are under intense scrutiny. Abnormal production or regulation of adipokines occurs in obese individuals and is implicated in the development of a variety of associated co-morbidities including metabolic syndrome, type 2 diabetes, atherosclerosis, heart disease, and cancer in people, although evaluation in domestic species is just beginning. Adipokines are now being examined as potential biomarkers for risk assessment for development of complications related to obesity. This article summarizes the function and regulation of some better-characterized adipokines. It also reviews the current information on the characterization of adipokines in some domestic species in which rates of obesity and obesity-related disorders are increasing, such as the dog, cat, and horse.
 ...
PMID:Adipokines: a review of biological and analytical principles and an update in dogs, cats, and horses. 1939 60