The availability of the human and mouse genome sequences has allowed the identification and comparison of their respective degradomes--the complete repertoire of proteases that are produced by these organisms. Because of the essential roles of proteolytic enzymes in the control of cell behaviour, survival and death, degradome analysis provides a useful framework for the global exploration of these protease-mediated functions in normal and pathological conditions.

Human and mouse proteases: a comparative genomic approach

Chronic obstructive pulmonary disease (COPD) is characterised by an inappropriate/excessive inflammatory response of the lungs to respiratory pollutants, mainly tobacco smoking. Recently, besides the typical pulmonary pathology of COPD (i.e. chronic bronchitis and emphysema), several effects occurring outside the lungs have been described, the so-called systemic effects of COPD. These effects are clinically relevant because they modify and can help in the classification and management of the disease. The present review discusses the following systemic effects of chronic obstructive pulmonary disease: 1) systemic inflammation; 2) nutritional abnormalities and weight loss; 3) skeletal muscle dysfunction; and 4) other potential systemic effects. For each of these, the potential mechanisms and clinical implications are discussed and areas requiring further research are highlighted.

https://erj.ersjournals.com/content/erj/21/2/347.full.pdf

Systemic effects of chronic obstructive pulmonary disease

Background: Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications.Purpose: The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD.Methods: An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological ...

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An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease

The current review presents the 2005 update of the human gene map for physical performance and health-related fitness phenotypes. It is based on peer-reviewed papers published by the end of 2005. The genes and markers with evidence of association or linkage with a performance or fitness phenotype in sedentary or active people, in adaptation to acute exercise, or for training-induced changes are positioned on the genetic map of all autosomes and the X chromosome. Negative studies are reviewed, but a gene or locus must be supported by at least one positive study before being inserted on the map. By the end of 2000, in the early version of the gene map, 29 loci were depicted. In contrast, the 2005 human gene map for physical performance and health-related phenotypes includes 165 autosomal gene entries and QTL, plus five others on the X chromosome. Moreover, there are 17 mitochondrial genes in which sequence variants have been shown to influence relevant fitness and performance phenotypes. Thus, the map is growing in complexity. Unfortunately, progress is slow in the field of genetics of fitness and performance, primarily because the number of laboratories and scientists focused on the role of genes and sequence variations in exercise-related traits continues to be quite limited.

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The human gene map for performance and health-related fitness phenotypes: the 2005 update.

Traditionally, chronic obstructive pulmonary disease (COPD) has been understood as a disease of the lungs, characterized by irreversible airflow limitation due to chronic bronchitis and/or emphysema The latter are thought mainly to be the consequence of an excessive inflammatory response to tobacco smoking Recently, several studies have shown that this pulmonary inflammation may also be detected in the systemic circulation, and that this systemic inflammation may have important clinical consequences Most prominent among them is the loss of skeletal muscle mass that a significant percentage of patients with COPD will show during the course of their disease This limits considerably their exercise capacity, jeopardizes their health status, and has a negative impact on their prognosis Importantly, such prognostic value is independent of the degree of airflow obstruction and potentially reversible with appropriate therapy This chapter summarizes available evidence supporting the concept that COPD is more than a lung disease (the systemic effects of COPD), and speculates on potential cellular mechanisms as future therapeutic targets

Systemic effects of chronic obstructive pulmonary disease.

Angiotensin-converting enzyme in human skeletal muscle1 can be encoded by either of two variants of the ACE gene2, one of which carries an insertion of 287 base pairs. This longer allele gives rise to lower enzyme activity2, and is associated with enhanced endurance performance3 and an anabolic response to intense exercise training4. Here we examine training-related changes in the mechanical efficiency of human skeletal muscle (energy used per unit power output) and find that the presence of this ACE allele confers an enhanced mechanical efficiency in trained muscle.

The ACE gene and muscle performance

Human physical performance is strongly influenced by genetic factors. We have previously reported that the I variant of the human angiotensin I-converting enzyme (ACE) gene is associated with greater endurance performance in mountaineers and Olympic runners and improved performance in army recruits. In this study we examined whether this effect is mediated by improvements in cardiovascular fitness with training in 58 army recruits homozygous for the insertion (I, ACE genotype II) or deletion (D, ACE genotype DD) allele. A submaximal and maximal exercise protocol was used to calculate both the heart rate/oxygen uptake (VO2) relationship and changes in maximal oxygen uptake (VO2max), respectively. There was no significant intergroup difference in VO2max at baseline (P=0.19) or after training (P=0.22). There was no difference between genotypes with training in the heart rate/VO2 elevation (P = 0.79 for the mean difference in mean adjusted heart rates). However, VO2 at all exercise intensities in the submaximal test was lower for all subjects after training and at 80 W the reduction in VO2 was greater for the II subjects compared to DD subjects [mean(SEM)] [1.6 (0.27) and 0.68 (0.27) ml kg(-1) min(-1), respectively; P = 0.02 for mean difference]. The I/D polymorphism may play a role in enhanced endurance performance but this is not mediated by differences in VO2max or the heart rate/VO2 relationship in response to training.

Endurance enhancement related to the human angiotensin I-converting enzyme I-D polymorphism is not due to differences in the cardiorespiratory response to training

Marianne Hayward

Papers

The ACE gene and muscle performance

Endurance enhancement related to the human angiotensin I-converting enzyme I-D polymorphism is not due to differences in the cardiorespiratory response to training